Kits or devices and methods for detecting hippocampal atrophy

Abstract

The present invention relates to: a kit or device for detecting hippocampal atrophy, the kit or device including a nucleic acid capable of binding specifically to predetermined miRNA, which is a marker for hippocampal atrophy, or to a complementary strand thereof; and a method for detecting hippocampal atrophy, the method including measuring the miRNA in vitro.

Description

[Technical Field]

[0001] The present invention relates to a kit or device for detecting hippocampal atrophy, comprising a specific miRNA or nucleic acid capable of specifically binding to its complementary strand, which can be used for examining hippocampal atrophy in the brain of a subject, and a method for detecting hippocampal atrophy, comprising measuring the expression level of said miRNA. [Background technology]

[0002] The hippocampus is a part of the limbic system, a brain organ located deep within the temporal lobe of the cerebral cortex. Its physiological functions are related to intellectual function, memory, and spatial awareness. The hippocampus plays a role in storing new memories (approximate memories) until they are consolidated into long-term memories. Therefore, atrophy or damage to the hippocampus impairs memory formation and leads to cognitive memory impairment.

[0003] Hippocampal atrophy is caused by the loss of nerve cells that make up the hippocampus. While it is known that the brain as a whole, including the hippocampus, atrophies with age, diseases other than aging that cause particularly significant atrophy of the hippocampus include Alzheimer's disease, frontotemporal lobar degeneration, depression, post-traumatic stress disorder, and schizophrenia.

[0004] The results of tests for the degree of hippocampal atrophy are treated as one piece of information (N: Neurodegeneration) in the diagnosis of Alzheimer's disease. Common methods for examining the hippocampus include imaging diagnostics such as brain MRI. In addition, FDG-PET, an imaging diagnostic method that measures glucose metabolism in the brain, may be usable as a method to measure neuronal cell death, which is a cause of hippocampal atrophy (Non-Patent Literature 1).

[0005] Progress is also being made in developing marker tests for diagnosing Alzheimer's disease, a disease characterized by hippocampal atrophy. For example, a minimally invasive method for measuring amyloid-beta, which is considered to be the cause of Alzheimer's disease, from a small amount of plasma using immunoprecipitation and mass spectrometry has been reported (Non-Patent Document 2). In addition, it has been reported that it is possible to detect Alzheimer's disease patients with a sensitivity of 81% and a specificity of 79% by measuring the expression levels of 451 types of miRNAs (hsa-miR-1228-5p, hsa-miR-6088, hsa-miR-4525, hsa-miR-4741, etc.) in serum samples as a blood test (Patent Document 1).

[0006] Similarly, there are reports that it is possible to detect Alzheimer's disease patients by measuring the expression levels of miRNAs such as hsa-miR-486-3p contained in blood components as a biochemical diagnostic method for neurodegenerative diseases such as Alzheimer's disease using nucleic acids (Patent Document 2).

[0007] Furthermore, there are reports that it is possible to detect Alzheimer's disease patients by measuring hsa-miR-6805-5p and other substances in blood samples (Patent Document 3).

[0008] It has been reported that patients with Alzheimer's disease and mild dementia can be detected by measuring hsa-miR-320b and other substances in blood samples (Patent Document 4).

[0009] Similarly, there are reports that the expression levels of miRNAs such as hsa-miR-663a in the serum are significantly reduced in Alzheimer's disease patients compared to healthy individuals (Non-Patent Literature 3).

[0010] It has been reported that it is possible to detect these substances by measuring hsa-miR-760 and hsa-miR-887-3p contained in cerebrospinal fluid (Patent Document 5).

[0011] It has been reported that dementia patients can be detected by measuring hsa-miR-4463 and other substances in a sample (Patent Document 6).

[0012] Similarly, it has been reported that it is possible to detect patients with Alzheimer's disease by measuring the expression levels of miRNAs such as hsa-miR-128-1-5p, hsa-miR-128-2-5p, hsa-miR-187-5p, hsa-miR-711, and hsa-miR-328-5p contained in microvesicles in body fluids, for the purpose of diagnosing neurodegenerative diseases such as Alzheimer's disease (Patent Document 7).

[0013] Similarly, there are reports that the expression levels of miRNAs such as hsa-miR-4674 and hsa-miR-6722-3p in brain tissue are significantly altered in patients with Alzheimer's disease (Non-Patent Literature 4).

[0014] Furthermore, regarding the effects of nucleic acids on nerve cells, there are reports that hsa-miR-204-3p is involved in the expression of proteins important for nerve cell formation (Non-Patent Literature 5).

[0015] Furthermore, regarding tau protein, which, like amyloid-beta, has been shown to be associated with Alzheimer's disease, there are reports that the total amount of tau in cerebrospinal fluid shows a high correlation (p<0.001) with the volume of the hippocampal / amygdala region quantified using software (FreeSurfer) on MRI images (Non-Patent Literature 6).

[0016] Dementia is generally progressive and involves irreversible degeneration of brain nerve cells; therefore, measuring the degree of hippocampal atrophy is an important diagnostic test for dementia. In order to provide medical interventions tailored to the patient's symptoms for dementia treatment, it is important to stratify patients according to the type of dementia based on pathological findings, and thus a diagnostic marker that can objectively and quantitatively measure the degree of hippocampal atrophy is required. However, the methods described in Patent Documents 1-7 and Non-Patent Documents 1-6 cannot be said to have sufficient performance as diagnostic methods for hippocampal atrophy, as will be discussed below.

[0017] First, MRI, a common brain imaging test, produces quantitative results that can vary depending on the imaging equipment, method, and the diagnosing physician. Therefore, there is no generalized index for hippocampal atrophy regarding the quantitative value of hippocampal volume. Furthermore, although MRI is widely used, some facilities lack the necessary equipment for brain MRI, and individuals with magnetic metals in their bodies or those with claustrophobia may find it difficult to undergo MRI. Thus, it is not universally accessible to everyone and lacks convenience. Non-patent document 1 introduces FDG-PET as a brain imaging test, but facilities capable of performing FDG-PET are limited in terms of equipment, and although safety is guaranteed, it carries the risk of using radioactive materials. As described above, brain imaging diagnostic methods for detecting hippocampal atrophy and synaptic degeneration mainly have problems in terms of convenience, safety, and quantitative accuracy for patients.

[0018] The testing method described in Non-Patent Literature 2 is limited to measurements using a mass spectrometer, requiring advanced measurement techniques. Furthermore, the mechanism by which the measured APP669-771 (amyloid-beta protein) fluctuates is unknown, and a direct correlation with hippocampal atrophy cannot be found.

[0019] Patent Document 1 defines Alzheimer's disease patients as positive based on a physician's diagnosis derived from the patient's clinical findings; therefore, stratified testing is not possible, and a direct correlation with hippocampal atrophy cannot be found from it. The same applies to Patent Documents 2-4, 6-7, and Non-Patent Document 3, which do not disclose a marker that can directly detect hippocampal atrophy.

[0020] The method described in Non-Patent Document 4 requires the use of brain tissue as a specimen and cannot be used as a simple test.

[0021] Non-patent document 5 does not directly demonstrate a link between the nucleic acid in question and hippocampal atrophy, and therefore it cannot be said that the disclosed miRNA can be used as a marker for hippocampal atrophy.

[0022] In the methods described in Patent Document 5 and Non-Patent Document 6, the collection of cerebrospinal fluid is highly invasive and burdensome to patients.

[0023] Although the method that directly shows the atrophy of the hippocampus is brain imaging examination, at the current stage, its use is limited in terms of patient burden and equipment, and its simplicity and versatility are low. In the screening prior to performing these image diagnoses, blood tests and the like are desirable as minimally invasive and simple biochemical diagnoses, but there is no method that can detect hippocampal atrophy with low invasiveness in the current marker tests. The development of a diagnostic marker that can correctly determine whether the hippocampus is atrophied using a blood specimen is desired.

Prior Art Documents

Patent Documents

[0024]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

[0026] The object of this invention is to provide a hippocampal atrophy marker that enables the detection of hippocampal atrophy without the need for MRI, and means and methods for objectively and effectively detecting hippocampal atrophy using this marker. [Means for solving the problem]

[0027] As a result of diligent research to solve the above problems, the inventors of this invention have discovered a hippocampal atrophy marker that can detect the degree of atrophy in the hippocampal region, which is closely related to dementia, and have completed the present invention based on this marker.

[0028] In other words, the present invention includes the following embodiments. (1) miR-3131, miR-6757-5p, miR-4706, miR-5001-5p, miR-3180-3p, miR-642b-3p, miR-4655-5p, miR-6819-5p, miR-937-5p, miR-4688, miR-6741-5p, miR-7107-5p, miR-4271, miR-1229-5p, miR-4707-5p, miR-6808-5p, miR-4656, miR-6076, miR-6762-5p, miR-7109-5p, miR-6732-5p, miR-3195, miR-7150, miR-642a-3p, miR-1249-5p, miR-3185, miR-4689, miR-3141, miR-6840-3p, miR-3135b, miR-1914-3p, miR-4446-3p, miR-4433b-3p, miR-6877-5p, miR-6848-5p, miR-3620-5p, miR-6825-5p, miR-5739, miR-3663-3p, miR-4695-5p, miR-3162-5p, miR-3679-5p, miR-8059, miR-7110-5p, miR-1275, miR-6779-5p, miR-197-5p, miR-6845-5p, miR-4327, miR-4723-5p, miR-4530, miR-6771-5p, miR-614, miR-92a-2-5p, miR-6891-5p, miR-6124, miR-4687-3p, miR-4442, miR-7977, miR-6785-5p, miR-4497, miR-8071, miR-663b, miR-3180, miR-4251, miR-1285-3p, miR-6870-5p, miR-4484, miR-4476, miR-6749-5p, miR-4454, miR-6893-5p, miR-6085, miR-4787-5p, miR-149-3p, miR-7704, miR-6125, miR-6090, miR-3197, miR-6850-5p, miR-4467, miR-6885-5p, miR-6803-5p, miR-6798-5p, miR-6780b-5p, miR-6768-5p, miR-5100, miR-6724-5p, miR-6879-5p, miR-7108-5p, miR-4649-5p,A kit for detecting hippocampal atrophy, comprising at least one polynucleotide selected from the group consisting of miR-4739, miR-6089, miR-1908-5p, miR-4516, miR-2861, miR-4492, miR-4294, miR-6791-5p, miR-1469, miR-6752-5p, miR-4730, miR-6126, miR-6869-5p, miR-1268a, miR-6799-5p, miR-8069, miR-3621, and miR-4763-3p, or a nucleic acid that can specifically bind to the complementary strand of said polynucleotide.

[0029] (2) The nucleic acid is a polynucleotide of the following (a) to (e): (a) A polynucleotide consisting of a nucleotide sequence represented by any of Sequence IDs 1 to 109, or a nucleotide sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides. (b) Polynucleotides comprising a base sequence represented by any of SEQ ID NOs: 1 to 109, variants thereof, derivatives thereof, or fragments thereof comprising 15 or more consecutive bases (c) A polynucleotide consisting of a nucleotide sequence represented by any of Sequence IDs 1 to 109 or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides. (d) A polynucleotide containing a nucleotide sequence represented by any of Sequence IDs 1 to 109 or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides, (e) A polynucleotide that hybridizes with any of the polynucleotides in (a) to (d) above under stringent conditions. The kit described in (1), which is a polynucleotide selected from the group consisting of the following.

[0030] (3) The kit is miR-1228-5p, miR-760, miR-187-5p, miR-7111-5p, miR-6088, miR-6805-3p, miR-4640-5p, miR-6721-5p, miR-6880-5p, miR-711, miR-128-1-5p, miR-4525, miR-486-3p, miR-6756-5p, miR-1260b, miR-3184-5p, miR-6075, miR-204-3p, miR-4728-5p, miR-4534, miR-4758-5p, miR-8063, miR-6836-3p, miR-6789-5p, miR-744-5p, miR-1909-3p, miR-887-3p, miR-4745-5p, miR-4433a-3p, miR-5090, miR-296-5p, miR-939-5p, miR-3648, miR-3196, miR-6722-3p, miR-6805-5p, miR-1202, miR-6775-5p, miR-6087, miR-6765-5p, miR-6875-5p, miR-4674, miR-1233-5p, miR-7114-5p, miR-5787, miR-8072, miR-3619-3p, miR-4632-5p, miR-6800-5p, miR-4634, miR-4486, miR-6727-5p, miR-4505, miR-4725-3p, miR-1538, miR-320b, miR-1915-5p, miR-328-5p, miR-6820-5p, miR-6726-5p, miR-3665, miR-638, miR-762, miR-4466, miR-3940-5p, miR-The kit according to (1) or (2), further comprising at least one polynucleotide selected from the group consisting of miR-3178 and miR-4463, or a nucleic acid that can specifically bind to the complementary strand of said polynucleotide.

[0031] (4) The nucleic acid is a polynucleotide of the following (f) to (j): (f) A polynucleotide consisting of a base sequence represented by any of sequence numbers 110 to 200, or a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases. (g) Polynucleotides containing a base sequence represented by any of SEQ ID NOs: 110-200, variants thereof, derivatives thereof, or fragments thereof containing 15 or more consecutive bases. (h) A polynucleotide consisting of a nucleotide sequence represented by any of sequence numbers 110 to 200 or a nucleotide sequence complementary to the nucleotide sequence in said sequence where u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides. (i) A polynucleotide containing a nucleotide sequence represented by any of SEQ ID NOs: 110-200 or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides, and (j) A polynucleotide that hybridizes with any of the polynucleotides in (f) to (i) above under stringent conditions. The kit described in (3) is a polynucleotide selected from the group consisting of the following.

[0032] (5) miR-3131, miR-6757-5p, miR-4706, miR-5001-5p, miR-3180-3p, miR-642b-3p, miR-4655-5p, miR-6819-5p, miR-937-5p, miR-4688, miR-6741-5p, miR-7107-5p, miR-4271, miR-1229-5p, miR-4707-5p, miR-6808-5p, miR-4656, miR-6076, miR-6762-5p, miR-7109-5p, miR-6732-5p, miR-3195, miR-7150, miR-642a-3p, miR-1249-5p, miR-3185, miR-4689, miR-3141, miR-6840-3p, miR-3135b, miR-1914-3p, miR-4446-3p, miR-4433b-3p, miR-6877-5p, miR-6848-5p, miR-3620-5p, miR-6825-5p, miR-5739, miR-3663-3p, miR-4695-5p, miR-3162-5p, miR-3679-5p, miR-8059, miR-7110-5p, miR-1275, miR-6779-5p, miR-197-5p, miR-6845-5p, miR-4327, miR-4723-5p, miR-4530, miR-6771-5p, miR-614, miR-92a-2-5p, miR-6891-5p, miR-6124, miR-4687-3p, miR-4442, miR-7977, miR-6785-5p, miR-4497, miR-8071, miR-663b, miR-3180, miR-4251, miR-1285-3p, miR-6870-5p, miR-4484, miR-4476, miR-6749-5p, miR-4454, miR-6893-5p, miR-6085, miR-4787-5p, miR-149-3p, miR-7704, miR-6125, miR-6090, miR-3197, miR-6850-5p, miR-4467, miR-6885-5p, miR-6803-5p, miR-6798-5p, miR-6780b-5p, miR-6768-5p, miR-5100, miR-6724-5p, miR-6879-5p, miR-7108-5p, miR-4649-5p,A device for detecting hippocampal atrophy, comprising at least one polynucleotide selected from the group consisting of miR-4739, miR-6089, miR-1908-5p, miR-4516, miR-2861, miR-4492, miR-4294, miR-6791-5p, miR-1469, miR-6752-5p, miR-4730, miR-6126, miR-6869-5p, miR-1268a, miR-6799-5p, miR-8069, miR-3621, and miR-4763-3p, or a nucleic acid that can specifically bind to the complementary strand of said polynucleotide.

[0033] (6) The nucleic acid is a polynucleotide of the following (a) to (e): (a) A polynucleotide consisting of a nucleotide sequence represented by any of Sequence IDs 1 to 109, or a nucleotide sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides. (b) Polynucleotides comprising a base sequence represented by any of SEQ ID NOs: 1 to 109, variants thereof, derivatives thereof, or fragments thereof comprising 15 or more consecutive bases (c) A polynucleotide consisting of a nucleotide sequence represented by any of Sequence IDs 1 to 109 or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides. (d) A polynucleotide containing a nucleotide sequence represented by any of Sequence IDs 1 to 109 or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides, (e) A polynucleotide that hybridizes with any of the polynucleotides in (a) to (d) above under stringent conditions. The device according to (5), which is a polynucleotide selected from the group consisting of the following.

[0034] (7) The device is miR-1228-5p, miR-760, miR-187-5p, miR-7111-5p, miR-6088, miR-6805-3p, miR-4640-5p, miR-6721-5p, miR-6880-5p, miR-711, miR-128-1-5p, miR-4525, miR-486-3p, miR-6756-5p, miR-1260b, miR-3184-5p, miR-6075, miR-204-3p, miR-4728-5p, miR-4534, miR-4758-5p, miR-8063, miR-6836-3p, miR-6789-5p, miR-744-5p, miR-1909-3p, miR-887-3p, miR-4745-5p, miR-4433a-3p, miR-5090, miR-296-5p, miR-939-5p, miR-3648, miR-3196, miR-6722-3p, miR-6805-5p, miR-1202, miR-6775-5p, miR-6087, miR-6765-5p, miR-6875-5p, miR-4674, miR-1233-5p, miR-7114-5p, miR-5787, miR-8072, miR-3619-3p, miR-4632-5p, miR-6800-5p, miR-4634, miR-4486, miR-6727-5p, miR-4505, miR-4725-3p, miR-1538, miR-320b, miR-1915-5p, miR-328-5p, miR-6820-5p, miR-6726-5p, miR-3665, miR-638, miR-762, miR-4466, miR-3940-5p, miR-1237-5p, miR-575, miR-3656, miR-4488, miR-4281, miR-6781-5p, miR-4532, miR-4665-5p, miR-6816-5p, miR-4508, miR-6784-5p, miR-6786-5p, miR-4741, miR-1343-5p, miR-1227-5p, miR-4734, miR-3960, miR-128-2-5p, miR-6743-5p, miR-663a, miR-6729-5p, miR-1915-3p, miR-1268b, miR-4651, which are another hippocampal atrophy marker.The device according to (5) or (6), further comprising at least one polynucleotide selected from the group consisting of miR-3178 and miR-4463, or a nucleic acid that can specifically bind to the complementary strand of said polynucleotide.

[0035] (8) The nucleic acid is a polynucleotide of the following (f) to (j): (f) A polynucleotide consisting of a base sequence represented by any of sequence numbers 110 to 200, or a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases. (g) Polynucleotides containing a base sequence represented by any of SEQ ID NOs: 110-200, variants thereof, derivatives thereof, or fragments thereof containing 15 or more consecutive bases. (h) A polynucleotide consisting of a nucleotide sequence represented by any of sequence numbers 110 to 200 or a nucleotide sequence complementary to the nucleotide sequence in said sequence where u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides. (i) A polynucleotide containing a nucleotide sequence represented by any of SEQ ID NOs: 110-200 or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides, and (j) A polynucleotide that hybridizes with any of the polynucleotides in (f) to (i) above under stringent conditions. The device according to (7), which is a polynucleotide selected from the group consisting of the following.

[0036] (9) The device described in any of (5) to (8), wherein the above device is a device for measurement by hybridization technology.

[0037] (10) The device described in (9), wherein the hybridization technology is nucleic acid array technology.

[0038] In the specimen of the subject, miR-3131, miR-6757-5p, miR-4706, miR-5001-5p, miR-3180-3p, miR-642b-3p, miR-4655-5p, miR-6819-5p, miR-937-5p, miR-4688, miR-6741-5p, miR-7107-5p, miR-4271, miR-1229-5p, miR-4707-5p, miR-6808-5p, miR-4656, miR-6076, miR-6762-5p, miR-7109-5p, miR-6732-5p, miR-3195, miR-7150, miR-642a-3p, miR-1249-5p, miR-3185, miR-4689, miR-3141, miR-6840-3p, miR-3135b, miR-1914-3p, miR-4446-3p, miR-4433b-3p, miR-6877-5p, miR-6848-5p, miR-3620-5p, miR-6825-5p, miR-5739, miR-3663-3p, miR-4695-5p, miR-3162-5p, miR-3679-5p, miR-8059, miR-7110-5p, miR-1275, miR-6779-5p, miR-197-5p, miR-6845-5p, miR-4327, miR-4723-5p, miR-4530, miR-6771-5p, miR-614, miR-92a-2-5p, miR-6891-5p, miR-6124, miR-4687-3p, miR-4442, miR-7977, miR-6785-5p, miR-4497, miR-8071, miR-663b, miR-3180, miR-4251, miR-1285-3p, miR-6870-5p, miR-4484, miR-4476, miR-6749-5p, miR-4454, miR-6893-5p, miR-6085, miR-4787-5p, miR-149-3p, miR-7704, miR-6125, miR-6090, miR-3197, miR-6850-5p, miR-4467, miR-6885-5p, miR-6803-5p, miR-6798-5p, miR-6780b-5p, miR-6768-5p, miR-5100, miR-6724-5p, miR-6879-5p, miR-7108-5p, which are hippocampal atrophy markersA method for detecting hippocampal atrophy, comprising measuring the expression level of at least one polynucleotide selected from the group consisting of miR-4649-5p, miR-4739, miR-6089, miR-1908-5p, miR-4516, miR-2861, miR-4492, miR-4294, miR-6791-5p, miR-1469, miR-6752-5p, miR-4730, miR-6126, miR-6869-5p, miR-1268a, miR-6799-5p, miR-8069, miR-3621, and miR-4763-3p, and using the measured expression level to evaluate whether or not the hippocampus of the subject is atrophied.

[0039] The method according to (11), wherein the expression level of the polynucleotide is measured using the kit described in any of (1) to (4) or the device described in any of (5) to (10).

[0040] (13) The method according to (12), comprising substituting the measured expression level of the polynucleotide into a discriminant formula, which is prepared using the expression levels of the polynucleotide in a sample from a subject known to have hippocampal atrophy and the expression levels of the polynucleotide in a sample from a subject known not to have hippocampal atrophy as training samples, and thereby evaluating whether the hippocampus is atrophied or not.

[0041] (14) The nucleic acid is a polynucleotide of the following (a) to (e): (a) A polynucleotide consisting of a nucleotide sequence represented by any of Sequence IDs 1 to 109, or a nucleotide sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides. (b) Polynucleotides comprising a base sequence represented by any of SEQ ID NOs: 1 to 109, variants thereof, derivatives thereof, or fragments thereof comprising 15 or more consecutive bases (c) A polynucleotide consisting of a nucleotide sequence represented by any of Sequence IDs 1 to 109 or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides. (d) A polynucleotide containing a nucleotide sequence represented by any of Sequence IDs 1 to 109 or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides, (e) A polynucleotide that hybridizes with any of the polynucleotides in (a) to (d) above under stringent conditions. The method according to (12) or (13), wherein the polynucleotide is selected from the group consisting of the following.

[0042] (15) 、miR-7111-5p、miR-6088、miR-6805-3p、miR-4640-5p、miR-6721-5p、miR -6880-5p、miR-711、miR-128-1-5p、miR-4525、miR-486-3p、miR-6756-5p 、miR-1260b、miR-3184-5p、miR-6075、miR-204-3p、miR-4728-5p、miR-453 4、miR-4758-5p、miR-8063、miR-6836-3p、miR-6789-5p、miR-744-5p、miR -1909-3p、miR-887-3p、miR-4745-5p、miR-4433a-3p、miR-5090、miR-296 -5p、miR-939-5p、miR-3648、miR-3196、miR-6722-3p、miR-6805-5p、miR- 1202、miR-6775-5p、miR-6087、miR-6765-5p、miR-6875-5p、miR-4674、miR -1233-5p、miR-7114-5p、miR-5787、miR-8072、miR-3619-3p、miR-4632-5 p、miR-6800-5p、miR-4634、miR-4486、miR-6727-5p、miR-4505、miR-4725 -3p、miR-1538、miR-320b、miR-1915-5p、miR-328-5p、miR-6820-5p、miR- 6726-5p、miR-3665、miR-638、miR-762、miR-4466、miR-3940-5p、miR-1237 -5p、miR-575、miR-3656、miR-4488、miR-4281、miR-6781-5p、miR-4532、m iR-4665-5p、miR-6816-5p、miR-4508、miR-6784-5p、miR-6786-5p、miR-4 741、miR-1343-5p、miR-1227-5p、miR-4734、miR-3960、miR-128-2-5p、mi R-6743-5p、miR-663a、miR-6729-5p、miR-1915-3p、miR-1268b、miR-4651、The method according to any one of (12) to (14), further comprising at least one polynucleotide selected from the group consisting of miR-3178 and miR-4463, or a nucleic acid that can specifically bind to the complementary chain of said polynucleotide.

[0043] (16) The nucleic acid is a polynucleotide of the following (f) to (j): (f) A polynucleotide consisting of a base sequence represented by any of sequence numbers 110 to 200, or a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases. (g) Polynucleotides containing a base sequence represented by any of SEQ ID NOs: 110-200, variants thereof, derivatives thereof, or fragments thereof containing 15 or more consecutive bases. (h) A polynucleotide consisting of a nucleotide sequence represented by any of sequence numbers 110 to 200 or a nucleotide sequence complementary to the nucleotide sequence in said sequence where u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides. (i) A polynucleotide containing a nucleotide sequence represented by any of SEQ ID NOs: 110-200 or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides, and (j) A polynucleotide that hybridizes with any of the polynucleotides in (f) to (i) above under stringent conditions. The method according to (15), wherein the polynucleotide is selected from the group consisting of the following.

[0044] (17) The method according to any one of (11) to (16), wherein the subject is a human.

[0045] (18) The method according to any one of (11) to (17), wherein the specimen is blood, serum, or plasma.

[0046] <Definition of Terms> The terms used herein have the following definitions:

[0047] Abbreviations such as nucleotide, polynucleotide, DNA, and RNA shall be used in accordance with the "Guidelines for the Preparation of Specifications Including Base Sequences or Amino Acid Sequences" (compiled by the Japan Patent Office) and common practice in the art.

[0048] In this specification, "polynucleotide" is used for nucleic acids that include RNA, DNA, and RNA / DNA (chimeras). DNA includes cDNA, genomic DNA, and synthetic DNA. RNA includes total RNA, mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA, non-coding RNA, and synthetic RNA. In this specification, "synthetic DNA" and "synthetic RNA" refer to DNA and RNA artificially produced, for example, using an automated nucleic acid synthesizer, based on a predetermined base sequence (which may be either a natural or non-natural sequence). In this specification, "non-natural sequence" is intended to be used in a broad sense and includes sequences that differ from the natural sequence, such as sequences containing one or more nucleotide substitutions, deletions, insertions, and / or additions (i.e., mutant sequences), sequences containing one or more modified nucleotides (i.e., modified sequences), etc. Furthermore, in this specification, polynucleotide is used interchangeably with nucleic acid. In this specification, polynucleotide contains two or more nucleotides.

[0049] In this specification, "fragment" refers to a polynucleotide having a continuous base sequence of a portion of a polynucleotide, and it is desirable that the fragment has a length of 15 bases or more, preferably 17 bases or more, and more preferably 19 bases or more.

[0050] In this specification, the term "gene" is used to include not only RNA and double-stranded DNA, but also each single-stranded DNA component, such as the positive (or sense) strand or complementary (or antisense) strand, that constitutes them. It is not particularly limited by length.

[0051] Therefore, in this specification, unless otherwise specified, "gene" includes any of the following: double-stranded DNA including human genomic DNA, single-stranded DNA (positive strand), single-stranded DNA (complementary strand) having a sequence complementary to the positive strand, cDNA, microRNA (miRNA), and fragments thereof, the human genome, and their transcripts. Furthermore, "gene" includes not only "genes" represented by a specific base sequence (or sequence number), but also "nucleic acids" that encode RNAs with biologically equivalent function to the RNA encoded by these genes, such as congeners (i.e., homologs or orthologs), variants such as gene polymorphisms, and derivatives. Specifically, "nucleic acids" that encode such congeners, variants, or derivatives can be said to be "nucleic acids" having a base sequence that hybridizes with any of the base sequences represented by sequence numbers 1 to 740 or a base sequence in which u is t under the stringent conditions described later. Note that "gene" does not distinguish between functional regions and may include, for example, expression regulatory regions, coding regions, exons, or introns. Furthermore, "genes" may be contained within cells, released outside cells and existing independently, or encapsulated within vesicles called exosomes.

[0052] In this specification, "exosome" refers to a vesicle enclosed in a lipid bilayer secreted by a cell. Exosomes originate from multivesicular endosomes and may contain biomolecules such as RNA, DNA, and proteins when released into the extracellular environment. Exosomes are known to be found in bodily fluids such as blood, serum, plasma, cerebrospinal fluid, and lymph.

[0053] In this specification, "transcript" refers to RNA synthesized using the DNA sequence of a gene as a template. RNA polymerase binds to a site called the promoter located upstream of the gene, and RNA is synthesized by attaching ribonucleotides to the 3' end in a manner complementary to the DNA base sequence. This RNA contains not only the gene itself, but also the entire sequence from the transcription start site to the end of the poly(A) sequence, including the expression regulatory region, coding region, exons, or introns.

[0054] Furthermore, in this specification, unless otherwise specified, "microRNA (miRNA)" refers to a non-coding RNA, typically 15-25 nucleotides long, that is transcribed as a hairpin-like RNA precursor, cleaved by a dsRNA-cleaving enzyme with RNase III cleavage activity, incorporated into a protein complex called RISC, and involved in the repression of mRNA translation. In addition, the term "miRNA" as used herein includes not only so-called "miRNAs" represented by a specific nucleotide sequence (or sequence number), but also their precursors (pre-miRNA, pri-miRNA), miRNAs with biologically equivalent function to the miRNA represented by that specific nucleotide sequence (or sequence number), such as its homologs or orthologs, variants such as genetic polymorphisms, and derivatives of "miRNA." Such precursors, congeners, mutants, or derivatives of "miRNA" can be specifically identified, for example, by "miRBase" (version 21), and include "miRNA" having a nucleotide sequence that hybridizes with the complementary sequence of any specific nucleotide sequence represented by SEQ ID NOs. 1 to 740 under the stringent conditions described later. "miRBase" (version 21) is a web-based database that provides miRNA nucleotide sequences, annotations, and target gene predictions (http: / / www.mirbase.org / ). All miRNAs registered in "miRBase" are either cloned, expressed in vivo, or shown to be undergoing processing. Furthermore, "miRNA" in this invention may also be the gene product of a miR gene, and such gene products include mature miRNA (e.g., 15-25 nucleotide or 19-25 nucleotide non-coding RNA involved in the translational repression of mRNA as described above) or miRNA precursors (e.g., pre-miRNA or pri-miRNA as described above).

[0055] In this specification, "probe" includes polynucleotides, such as polynucleotides and / or complementary polynucleotides used to specifically detect RNA produced by gene expression or polynucleotides derived therefrom.

[0056] In this specification, “primer” includes a sequence of polynucleotides and / or complementary polynucleotides that specifically recognize (i.e., specifically bind to) and amplify a polynucleotide, such as RNA produced by gene expression or a polynucleotide derived therefrom.

[0057] Here, "complementary polynucleotide" (reverse chain) means a polynucleotide that is nucleotide-complementary based on base pairings such as A:T(U) and G:C to a full-length sequence of a polynucleotide consisting of a base sequence defined by any of sequence numbers 1 to 740, or a base sequence in which u is t, or a partial sequence thereof (for convenience, this will be called the forward chain). However, such "complementary polynucleotide" is not limited to cases where it forms a perfectly complementary sequence with the base sequence of the target forward chain, but may also have a complementary relationship to the target forward chain to the extent that it can hybridize under stringent conditions.

[0058] In this specification, "complementary strand" means a single-stranded polynucleotide consisting of a base sequence that is completely (at a 100% level) complementary to a particular single-stranded polynucleotide.

[0059] In this specification, "stringent conditions" refer to conditions under which a polynucleotide, such as a nucleic acid probe or nucleic acid primer, hybridizes to its target polynucleotide to a detectably greater extent (e.g., a measurement of the mean of the background measurement + standard error of the background measurement × 2 or more) than to other polynucleotides. Stringent conditions are sequence-dependent and vary depending on the environment in which hybridization takes place. By controlling the stringency of the hybridization and / or washing conditions, a target polynucleotide that is complementary (e.g., 100% complementary) to the polynucleotide can be defined. Specific examples of "stringent conditions" will be described later.

[0060] In this specification, "Tm value" refers to the temperature at which the double-stranded portion of a polynucleotide denatures into a single-stranded portion, and in which the double-stranded and single-stranded portions exist in a 1:1 ratio.

[0061] In this specification, "mutant" may refer to a nucleic acid, in the case of a natural mutant resulting from polymorphism, mutation, etc., or a mutant containing the deletion, substitution, addition, or insertion of 1, 2, 3 or more (e.g., 1 to several) bases in a nucleotide sequence represented by an SEQ ID NO: sequence number (in this invention, for example, any of SEQ ID NOs: 1 to 740), or a nucleotide sequence in which u is t, or a subsequence thereof, or a mutant containing the deletion, substitution, addition, or insertion of 1 or more bases in a premature miRNA of the nucleotide sequence of the SEQ ID NO: sequence, or a nucleotide sequence in which u is t, or a subsequence thereof, or a mutant showing approximately 90% or more, approximately 95% or more, approximately 97% or more, approximately 98% or more, or approximately 99% or more % identity with each of the nucleotide sequences or subsequences thereof, or a mutant that is a nucleic acid that hybridizes with a polynucleotide or oligonucleotide containing the nucleotide sequence or subsequence thereof under the stringent conditions defined above. In this specification, oligonucleotide means a polynucleotide with a length of 2 to 100 nucleotides.

[0062] In this specification, “several” or “several kinds” means about 10, 9, 8, 7, 6, 5, 4, 3 or 2 integers or kinds.

[0063] In this specification, mutants can be produced using well-known techniques such as site-directed mutagenesis and PCR-based mutagenesis.

[0064] In this specification, "% identity" can be determined with or without introducing gaps using protein or gene search systems such as BLAST (https: / / blast.ncbi.nlm.nih.gov / Blast.cgi) or FASTA (http: / / www.genome.jp / tools / fasta / ) (Zheng Zhang et al., 2000, J. Comput. Biol., vol. 7, pp. 203-214; Altschul, SF et al., 1990, Journal of Molecular Biology, vol. 215, pp. 403-410; Pearson, WR et al., 1988, Proc. Natl. Acad. Sci. USA, vol. 85, pp. 2444-2448).

[0065] In this specification, "derivative" means modified nucleic acids, non-limited derivatives labeled with, for example, fluorophores, modified nucleotides (e.g., nucleotides containing halogens, alkyl groups such as methyl, alkoxy groups such as methoxy, thio, carboxymethyl, etc., and derivatives including nucleotides that have undergone base reconfiguration, double bond saturation, deamination, substitution of oxygen molecules with sulfur molecules, etc.), PNA (peptide nucleic acid; Nielsen, PE et al., 1991, Science, Vol. 254, pp. 1497-500), LNA (locked nucleic acid; Obika, S. et al., 1998, Tetrahedron Lett., Vol. 39, pp. 5401-5404), etc.

[0066] In this specification, a polynucleotide selected from the group of miRNAs that are hippocampal atrophy markers, or a "nucleic acid" that can specifically bind to the complementary strand of said polynucleotide, is a synthesized or prepared nucleic acid, and specifically includes a "nucleic acid probe" or "primer." Such nucleic acids can be used directly or indirectly to detect the presence or absence of hippocampal atrophy in a subject, to diagnose the presence or absence and degree of improvement of hippocampal atrophy, to assess sensitivity to treatment for hippocampal atrophy, or to screen for candidate substances useful for the prevention, improvement, or treatment of hippocampal atrophy. Such nucleic acids include oligonucleotides and polynucleotides that can specifically recognize and bind to transcripts or cDNA synthetic nucleic acids consisting of any of the base sequences represented by SEQ ID NOs: 1 to 740 related to hippocampal atrophy, or their complementary strands, in vivo, particularly in body fluids such as blood and urine. Based on the above properties, these polynucleotides can be effectively used as probes for detecting the above-mentioned genes / miRNAs expressed in vivo, in tissues, or within cells, and as primers for amplifying the above-mentioned genes / miRNAs expressed in vivo.

[0067] As used herein, the term “detection” may be replaced by the terms “inspection,” “measurement,” “detection,” or “assessment support.” Furthermore, as used herein, the term “assessment” includes supporting a diagnosis or assessment based on inspection or measurement results.

[0068] As used herein, "subject" refers to mammals including humans, primates such as chimpanzees and gorillas, pet animals such as dogs and cats, domestic animals such as cows, horses, sheep and goats, rodents such as mice and rats, and animals kept in zoos. The preferred subject is human. Also, "subjects with a normal hippocampus," "subjects with atrophied hippocampus," and "subjects without atrophied hippocampus" also refer to mammals such as humans unless otherwise specified. things This means that subjects with a normal hippocampus, subjects with atrophied hippocampus, and subjects without atrophied hippocampus are all considered human. While the terms "subject" and "patient" can be used interchangeably, a more typical "patient" is a human.

[0069] As used herein, the hippocampus is a cortical region located in the medial part of the temporal lobe of the cerebrum, at the base of the inferior horn of the lateral ventricle, and is essential for the formation of explicit memories such as episodic memories.

[0070] As used herein, "atrophy" refers to a condition in which the volume of an organ or tissue that has grown to a normal volume is reduced due to various causes. As used herein, "hippocampal atrophy" means a reduction in the size of the hippocampus to the extent that it negatively affects its function. Hippocampal atrophy typically refers to a reduction in the volume of the hippocampus to the extent that its volume as a percentage of the whole brain is 0.6% or less. As mentioned above, hippocampal atrophy generally progresses gradually with age. Diseases that cause hippocampal atrophy other than aging include, but are not limited to, Alzheimer's disease, frontotemporal dementia, depression, post-traumatic stress disorder, and schizophrenia.

[0071] As used herein, "hippocampal atrophy" refers to the degree of hippocampal atrophy in a patient, and can be determined using the percentage of hippocampal volume relative to the whole brain as an indicator.

[0072] As used herein, "patients with non-atrophic hippocampus" includes those whose hippocampal volume ratio to total brain volume (the ratio of hippocampal volume to total brain volume) is 0.63% or higher, 0.64% or higher, 0.68% or higher, or 0.86% or higher.

[0073] As used herein, "patients with hippocampal atrophy" includes those whose hippocampal volume ratio to total brain volume is 0.60% or less, 0.59% or less, 0.57% or less, or 0.38% or less.

[0074] As used herein, "Alzheimer's disease" and "dementia palliative care" refer to dementia characterized by the accumulation of amyloid-beta and phosphorylated tau in the brain, and by neurodegeneration that leads to hippocampal atrophy.

[0075] As used herein, "mild cognitive impairment patient" refers to a patient who shows signs of dementia but has not yet developed it, specifically a patient with a Mindset for Scholastic Dementia Examination (MMSE) score of 25 or less.

[0076] As used herein, "P" or "P-value" refers to the probability in a statistical test that a statistic more extreme than the statistic actually calculated from the data under the null hypothesis is observed. Therefore, a smaller "P" or "P-value" indicates a statistically significant difference between the comparison groups.

[0077] In this specification, "sensitivity" refers to the value of (number of true positives) / (number of true positives + number of false negatives). Higher sensitivity allows for the early detection of hippocampal atrophy, enabling early medical intervention.

[0078] In this specification, "specificity" means (number of true negatives) / (number of true negatives + number of false positives). High specificity prevents unnecessary additional testing due to misidentification of non-hippocampal atrophy patients (healthy individuals) with normal cognitive function as hippocampal atrophy patients, leading to reduced burden on patients and lower medical costs.

[0079] In this specification, "precision" refers to the value of (number of true positives + number of true negatives) / (total number of cases). Precision indicates the proportion of all samples for which the discrimination result was correct, and is the primary indicator for evaluating discrimination performance.

[0080] In this specification, "R 2 " is the square of the correlation coefficient R. The correlation coefficient R is an indicator that shows the correlation between two variables.

[0081] In this specification, "RMSE" is an abbreviation for root mean squared error, and is one of the indicators used to evaluate the error of a regression model. The closer the observed values ​​are to the predicted values, the smaller the RMSE.

[0082] In this specification, "MAE" is an abbreviation for mean absolute error, and like RMSE, it is one of the indicators used to evaluate the error of a regression model. It decreases as the observed and predicted values ​​get closer together.

[0083] In this specification, the term "specimen" subject to determination, detection, or diagnosis refers to tissues and biomaterials in which the expression levels of the hippocampal atrophy marker gene / miRNA of the present invention may change in accordance with the presence or absence of hippocampal atrophy, the progression of hippocampal atrophy, and the exertion of therapeutic effects against hippocampal atrophy. Specifically, specimens may include brain tissue and nerve cells, nerve tissue, cerebrospinal fluid, bone marrow fluid, organs, skin, and bodily fluids such as blood, urine, saliva, sweat, and tissue exudate, as well as serum, plasma, feces, and hair prepared from blood. Furthermore, samples extracted from these may specifically be RNA or miRNA.

[0084] As used herein, the terms "hsa-miR-3131 gene" or "hsa-miR-3131" include the hsa-miR-3131 gene described in Sequence ID No. 1 (miRBase Accession No. MIMAT0014996) and other species homologs or orthologs. The hsa-miR-3131 gene can be obtained by the method described by Stark MS et al., 2010, PLoS One, Vol. 5, e9685. In addition, "hsa-miR-3131" is known to have a hairpin-like structure as its precursor, "hsa-mir-3131" (miRBase Accession No. MI0014151, Sequence ID No. 201).

[0085] As used herein, the terms "hsa-miR-6757-5p gene" or "hsa-miR-6757-5p" include the hsa-miR-6757-5p gene (miRBase Accession No. MIMAT0027414) described in Sequence ID No. 2, as well as other species homologs or orthologs. The hsa-miR-6757-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6757-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6757" (miRBase Accession No. MI0022602, Sequence ID No. 202).

[0086] As used herein, the terms "hsa-miR-4706 gene" or "hsa-miR-4706" include the hsa-miR-4706 gene (miRBase Accession No. MIMAT0019806) described in Sequence ID No. 3, as well as other species homologs or orthologs. The hsa-miR-4706 gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4706" is known to have a hairpin-like structure as its precursor, "hsa-mir-4706" (miRBase Accession No. MI0017339, Sequence ID No. 203).

[0087] As used herein, the terms "hsa-miR-5001-5p gene" or "hsa-miR-5001-5p" include the hsa-miR-5001-5p gene (miRBase Accession No. MIMAT0021021) described in Sequence ID No. 4, as well as other species homologs or orthologs. The hsa-miR-5001-5p gene can be obtained by the method described by Hansen TB et al., 2011, RNA Biol, Vol. 8, pp. 378-383. In addition, "hsa-miR-5001-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-5001" (miRBase Accession No. MI0017867, Sequence ID No. 204).

[0088] As used herein, the terms “hsa-miR-3180-3p gene” or “hsa-miR-3180-3p” include the hsa-miR-3180-3p gene (miRBase Accession No. MIMAT0015058) described in Sequence ID No. 5, as well as other species homologs or orthologs. The hsa-miR-3180-3p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Furthermore, "hsa-miR-3180-3p" is known to have hairpin-like precursors, "hsa-mir-3180-1, hsa-mir-3180-2, and hsa-mir-3180-3" (miRBase Accession No. MI0014214, MI0014215, MI0014217, SEQ ID NOs. 205, 206, and 207).

[0089] As used herein, the terms "hsa-miR-642b-3p gene" or "hsa-miR-642b-3p" include the hsa-miR-642b-3p gene (miRBase Accession No. MIMAT0018444) described in Sequence ID No. 6, as well as other species homologs or orthologs. The hsa-miR-642b-3p gene can be obtained by the method described by Witten D et al., 2010, BMC Biol, Vol. 8, p. 58. In addition, "hsa-miR-642b-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-642b" (miRBase Accession No. MI0016685, Sequence ID No. 208).

[0090] As used herein, the terms "hsa-miR-4655-5p gene" or "hsa-miR-4655-5p" include the hsa-miR-4655-5p gene (miRBase Accession No. MIMAT0019721) described in Sequence ID No. 7, as well as other species homologs or orthologs. The hsa-miR-4655-5p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4655-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4655" (miRBase Accession No. MI0017283, Sequence ID No. 209).

[0091] As used herein, the terms "hsa-miR-6819-5p gene" or "hsa-miR-6819-5p" include the hsa-miR-6819-5p gene (miRBase Accession No. MIMAT0027538) described in Sequence ID No. 8, as well as other species homologs or orthologs. The hsa-miR-6819-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6819-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6819" (miRBase Accession No. MI0022664, Sequence ID No. 210).

[0092] As used herein, the terms "hsa-miR-937-5p gene" or "hsa-miR-937-5p" include the hsa-miR-937-5p gene (miRBase Accession No. MIMAT0022938) described in Sequence ID No. 9, as well as other species homologs or orthologs. The hsa-miR-937-5p gene can be obtained by the method described by Lui WO et al., 2007, Cancer Res, Vol. 67, pp. 6031-6043. In addition, "hsa-miR-937-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-937" (miRBase Accession No. MI0005759, Sequence ID No. 211).

[0093] As used herein, the terms "hsa-miR-4688 gene" or "hsa-miR-4688" include the hsa-miR-4688 gene (miRBase Accession No. MIMAT0019777) described in Sequence ID No. 10, as well as other species homologs or orthologs. The hsa-miR-4688 gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4688" is known to have a hairpin-like structure as its precursor, "hsa-mir-4688" (miRBase Accession No. MI0017321, Sequence ID No. 212).

[0094] As used herein, the terms "hsa-miR-6741-5p gene" or "hsa-miR-6741-5p" include the hsa-miR-6741-5p gene (miRBase Accession No. MIMAT0027383) described in Sequence ID No. 11, as well as other species homologs or orthologs. The hsa-miR-6741-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6741-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6741" (miRBase Accession No. MI0022586, Sequence ID No. 213).

[0095] As used herein, the terms "hsa-miR-7107-5p gene" or "hsa-miR-7107-5p" include the hsa-miR-7107-5p gene (miRBase Accession No. MIMAT0028111) described in Sequence ID No. 12, as well as other species homologs or orthologs. The hsa-miR-7107-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-7107" is known to have a hairpin-like structure as its precursor, "hsa-mir-7107" (miRBase Accession No. MI0022958, Sequence ID No. 214).

[0096] As used herein, the terms "hsa-miR-4271 gene" or "hsa-miR-4271" include the hsa-miR-4271 gene (miRBase Accession No. MIMAT0016901) described in Sequence ID No. 13, as well as other species homologs or orthologs. The hsa-miR-4271 gene can be obtained by the method described by Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, "hsa-miR-4271" is known to have a hairpin-like structure as its precursor, "hsa-mir-4271" (miRBase Accession No. MI0015879, Sequence ID No. 215).

[0097] As used herein, the terms "hsa-miR-1229-5p gene" or "hsa-miR-1229-5p" include the hsa-miR-1229-5p gene (miRBase Accession No. MIMAT0022942) described in Sequence ID No. 14, as well as other species homologs or orthologs. The hsa-miR-1229-5p gene can be obtained by the method described by Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. In addition, "hsa-miR-1229-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1229" (miRBase Accession No. MI0006319, Sequence ID No. 216).

[0098] As used herein, the terms "hsa-miR-4707-5p gene" or "hsa-miR-4707-5p" include the hsa-miR-4707-5p gene (miRBase Accession No. MIMAT0019807) described in Sequence ID No. 15, as well as other species homologs or orthologs. The hsa-miR-4707-5p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4707-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4707" (miRBase Accession No. MI0017340, Sequence ID No. 217).

[0099] As used herein, the terms "hsa-miR-6808-5p gene" or "hsa-miR-6808-5p" include the hsa-miR-6808-5p gene (miRBase Accession No. MIMAT0027516) described in Sequence ID No. 16, as well as other species homologs or orthologs. The hsa-miR-6808-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6808" is known to have a hairpin-like structure as its precursor, "hsa-mir-6808" (miRBase Accession No. MI0022653, Sequence ID No. 218).

[0100] As used herein, the terms "hsa-miR-4656 gene" or "hsa-miR-4656" include the hsa-miR-4656 gene (miRBase Accession No. MIMAT0019723) described in Sequence ID No. 17, as well as other species homologs or orthologs. The hsa-miR-4656 gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4656" is known to have a hairpin-like structure as its precursor, "hsa-mir-4656" (miRBase Accession No. MI0017284, Sequence ID No. 219).

[0101] As used herein, the terms "hsa-miR-6076 gene" or "hsa-miR-6076" include the hsa-miR-6076 gene (miRBase Accession No. MIMAT0023701) described in Sequence ID No. 18, as well as other species homologs or orthologs. The hsa-miR-6076 gene can be obtained by the method described by Voellenkle C et al., 2012, RNA, Vol. 18, pp. 472-484. In addition, "hsa-miR-6076" is known to have a hairpin-like structure as its precursor, "hsa-mir-6076" (miRBase Accession No. MI0020353, Sequence ID No. 220).

[0102] As used herein, the terms "hsa-miR-6762-5p gene" or "hsa-miR-6762-5p" include the hsa-miR-6762-5p gene (miRBase Accession No. MIMAT0027424) described in Sequence ID No. 19, as well as other species homologs or orthologs. The hsa-miR-6762-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6762-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6762" (miRBase Accession No. MI0022607, Sequence ID No. 221).

[0103] As used herein, the terms "hsa-miR-7109-5p gene" or "hsa-miR-7109-5p" include the hsa-miR-7109-5p gene (miRBase Accession No. MIMAT0028115) described in Sequence ID No. 20, as well as other species homologs or orthologs. The hsa-miR-7109-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-7109" is known to have a hairpin-like structure as its precursor, "hsa-mir-7109" (miRBase Accession No. MI0022960, Sequence ID No. 222).

[0104] As used herein, the terms "hsa-miR-6732-5p gene" or "hsa-miR-6732-5p" include the hsa-miR-6732-5p gene (miRBase Accession No. MIMAT0027365) described in Sequence ID No. 21, as well as other species homologs or orthologs. The hsa-miR-6732-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6732-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6732" (miRBase Accession No. MI0022577, Sequence ID No. 223).

[0105] As used herein, the terms "hsa-miR-3195 gene" or "hsa-miR-3195" include the hsa-miR-3195 gene (miRBase Accession No. MIMAT0015079) described in Sequence ID No. 22, as well as other species homologs or orthologs. The hsa-miR-3195 gene can be obtained by the method described by Stark MS et al., 2010, PLoS One, Vol. 5, e9685. In addition, "hsa-miR-3195" is known to have a hairpin-like structure as its precursor, "hsa-mir-3195" (miRBase Accession No. MI0014240, Sequence ID No. 224).

[0106] As used herein, the terms "hsa-miR-7150 gene" or "hsa-miR-7150" include the hsa-miR-7150 gene (miRBase Accession No. MIMAT0028211) described in Sequence ID No. 23, as well as other species homologs or orthologs. The hsa-miR-7150 gene can be obtained by the method described by Oulas A et al., 2009, Nucleic Acids Res, Vol. 37, pp. 3276-3287. In addition, "hsa-miR-7150" is known to have a hairpin-like structure as its precursor, "hsa-mir-7150" (miRBase Accession No. MI0023610, Sequence ID No. 225).

[0107] As used herein, the terms "hsa-miR-642a-3p gene" or "hsa-miR-642a-3p" include the hsa-miR-642a-3p gene (miRBase Accession No. MIMAT0020924) described in Sequence ID No. 24, as well as other species homologs or orthologs. The hsa-miR-642a-3p gene can be obtained by the method described by Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. In addition, "hsa-miR-642a-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-642a" (miRBase Accession No. MI0003657, Sequence ID No. 226).

[0108] As used herein, the terms "hsa-miR-1249-5p gene" or "hsa-miR-1249-5p" include the hsa-miR-1249-5p gene (miRBase Accession No. MIMAT0032029) described in Sequence ID No. 25, as well as other species homologs or orthologs. The hsa-miR-1249-5p gene can be obtained by the method described by Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. In addition, "hsa-miR-1249-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1249" (miRBase Accession No. MI0006384, Sequence ID No. 227).

[0109] As used herein, the terms "hsa-miR-3185 gene" or "hsa-miR-3185" include the hsa-miR-3185 gene (miRBase Accession No. MIMAT0015065) described in Sequence ID No. 26, as well as other species homologs or orthologs. The hsa-miR-3185 gene can be obtained by the method described by Stark MS et al., 2010, PLoS One, Vol. 5, e9685. In addition, "hsa-miR-3185" is known to have a hairpin-like structure as its precursor, "hsa-mir-3185" (miRBase Accession No. MI0014227, Sequence ID No. 228).

[0110] As used herein, the terms "hsa-miR-4689 gene" or "hsa-miR-4689" include the hsa-miR-4689 gene (miRBase Accession No. MIMAT0019778) described in Sequence ID No. 27, as well as other species homologs or orthologs. The hsa-miR-4689 gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4689" is known to have a hairpin-like structure as its precursor, "hsa-mir-4689" (miRBase Accession No. MI0017322, Sequence ID No. 229).

[0111] As used herein, the terms "hsa-miR-3141 gene" or "hsa-miR-3141" include the hsa-miR-3141 gene (miRBase Accession No. MIMAT0015010) described in Sequence ID No. 28, as well as other species homologs or orthologs. The hsa-miR-3141 gene can be obtained by the method described by Stark MS et al., 2010, PLoS One, Vol. 5, e9685. In addition, "hsa-miR-3141" is known to have a hairpin-like structure as its precursor, "hsa-mir-3141" (miRBase Accession No. MI0014165, Sequence ID No. 230).

[0112] As used herein, the terms "hsa-miR-6840-3p gene" or "hsa-miR-6840-3p" include the hsa-miR-6840-3p gene (miRBase Accession No. MIMAT0027583) described in Sequence ID No. 29, as well as other species homologs or orthologs. The hsa-miR-6840-3p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6840-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6840" (miRBase Accession No. MI0022686, Sequence ID No. 231).

[0113] As used herein, the terms "hsa-miR-3135b gene" or "hsa-miR-3135b" include the hsa-miR-3135b gene (miRBase Accession No. MIMAT0018985) described in Sequence ID No. 30, as well as other species homologs or orthologs. The hsa-miR-3135b gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-3135b" is known to have a hairpin-like structure as its precursor, "hsa-mir-3135b" (miRBase Accession No. MI0016809, Sequence ID No. 232).

[0114] As used herein, the terms "hsa-miR-1914-3p gene" or "hsa-miR-1914-3p" include the hsa-miR-1914-3p gene (miRBase Accession No. MIMAT0007890) described in Sequence ID No. 31, as well as other species homologs or orthologs. The hsa-miR-1914-3p gene can be obtained by the method described by Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. In addition, "hsa-miR-1914-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1914" (miRBase Accession No. MI0008335, Sequence ID No. 233).

[0115] As used herein, the terms "hsa-miR-4446-3p gene" or "hsa-miR-4446-3p" include the hsa-miR-4446-3p gene (miRBase Accession No. MIMAT0018965) described in Sequence ID No. 32, as well as other species homologs or orthologs. The hsa-miR-4446-3p gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4446-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4446" (miRBase Accession No. MI0016789, Sequence ID No. 234).

[0116] As used herein, the terms "hsa-miR-4433b-3p gene" or "hsa-miR-4433b-3p" include the hsa-miR-4433b-3p gene (miRBase Accession No. MIMAT0030414) described in Sequence ID No. 33, as well as other species homologs or orthologs. The hsa-miR-4433b-3p gene can be obtained by the method described by Ple H et al., 2012, PLoS One, Vol. 7, e50746. In addition, "hsa-miR-4433b-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4433b" (miRBase Accession No. MI0025511, Sequence ID No. 235).

[0117] As used herein, the terms "hsa-miR-6877-5p gene" or "hsa-miR-6877-5p" include the hsa-miR-6877-5p gene (miRBase Accession No. MIMAT0027654) described in Sequence ID No. 34, as well as other species homologs or orthologs. The hsa-miR-6877-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6877-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6877" (miRBase Accession No. MI0022724, Sequence ID No. 236).

[0118] As used herein, the terms "hsa-miR-6848-5p gene" or "hsa-miR-6848-5p" include the hsa-miR-6848-5p gene (miRBase Accession No. MIMAT0027596) described in Sequence ID No. 35, as well as other species homologs or orthologs. The hsa-miR-6848-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6848-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6848" (miRBase Accession No. MI0022694, Sequence ID No. 237).

[0119] As used herein, the terms "hsa-miR-3620-5p gene" or "hsa-miR-3620-5p" include the hsa-miR-3620-5p gene (miRBase Accession No. MIMAT0022967) described in Sequence ID No. 36, as well as other species homologs or orthologs. The hsa-miR-3620-5p gene can be obtained by the method described by Witten D et al., 2010, BMC Biol, Vol. 8, p. 58. In addition, "hsa-miR-3620-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3620" (miRBase Accession No. MI0016011, Sequence ID No. 238).

[0120] As used herein, the terms "hsa-miR-6825-5p gene" or "hsa-miR-6825-5p" include the hsa-miR-6825-5p gene (miRBase Accession No. MIMAT0027550) described in Sequence ID No. 37, as well as other species homologs or orthologs. The hsa-miR-6825-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6825-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6825" (miRBase Accession No. MI0022670, Sequence ID No. 239).

[0121] As used herein, the terms "hsa-miR-5739 gene" or "hsa-miR-5739" include the hsa-miR-5739 gene (miRBase Accession No. MIMAT0023116) described in Sequence ID No. 38, as well as other species homologs or orthologs. The hsa-miR-5739 gene can be obtained by the method described by Yoo JK et al., 2011, Biochem Biophys Res Commun., Vol. 415, pp. 258-262. In addition, "hsa-miR-5739" is known to have a hairpin-like structure as its precursor, "hsa-mir-5739" (miRBase Accession No. MI0019412, Sequence ID No. 240).

[0122] As used herein, the terms "hsa-miR-3663-3p gene" or "hsa-miR-3663-3p" include the hsa-miR-3663-3p gene (miRBase Accession No. MIMAT0018085) described in Sequence ID No. 39, as well as other species homologs or orthologs. The hsa-miR-3663-3p gene can be obtained by the method described by Liao JY et al., 2010, PLoS One, Vol. 5, e10563. In addition, "hsa-miR-3663-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3663" (miRBase Accession No. MI0016064, Sequence ID No. 241).

[0123] As used herein, the terms "hsa-miR-4695-5p gene" or "hsa-miR-4695-5p" include the hsa-miR-4695-5p gene (miRBase Accession No. MIMAT0019788) described in Sequence ID No. 40, as well as other species homologs or orthologs. The hsa-miR-4695-5p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4695-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4695" (miRBase Accession No. MI0017328, Sequence ID No. 242).

[0124] As used herein, the terms "hsa-miR-3162-5p gene" or "hsa-miR-3162-5p" include the hsa-miR-3162-5p gene (miRBase Accession No. MIMAT0015036) described in Sequence ID No. 41, as well as other species homologs or orthologs. The hsa-miR-3162-5p gene can be obtained by the method described by Stark MS et al., 2010, PLoS One, Vol. 5, e9685. In addition, "hsa-miR-3162-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3162" (miRBase Accession No. MI0014192, Sequence ID No. 243).

[0125] As used herein, the terms "hsa-miR-3679-5p gene" or "hsa-miR-3679-5p" include the hsa-miR-3679-5p gene (miRBase Accession No. MIMAT0018104) described in Sequence ID No. 42, as well as other species homologs or orthologs. The hsa-miR-3679-5p gene can be obtained by the method described by Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. In addition, "hsa-miR-3679-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3679" (miRBase Accession No. MI0016080, Sequence ID No. 244).

[0126] As used herein, the terms "hsa-miR-8059 gene" or "hsa-miR-8059" include the hsa-miR-8059 gene described in Sequence ID No. 43 (miRBase Accession No. MIMAT0030986) and other species homologs or orthologs. The hsa-miR-8059 gene can be obtained by the method described by Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. In addition, "hsa-miR-8059" is known to have a hairpin-like structure as its precursor, "hsa-mir-8059" (miRBase Accession No. MI0025895, Sequence ID No. 245).

[0127] As used herein, the terms "hsa-miR-7110-5p gene" or "hsa-miR-7110-5p" include the hsa-miR-7110-5p gene (miRBase Accession No. MIMAT0028117) described in Sequence ID No. 44, as well as other species homologs or orthologs. The hsa-miR-7110-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-7110-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7110" (miRBase Accession No. MI0022961, Sequence ID No. 246).

[0128] As used herein, the terms "hsa-miR-1275 gene" or "hsa-miR-1275" include the hsa-miR-1275 gene (miRBase Accession No. MIMAT0005929) described in Sequence ID No. 45, as well as other species homologs or orthologs. The hsa-miR-1275 gene can be obtained by the method described by Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. In addition, "hsa-miR-1275" is known to have a hairpin-like structure as its precursor, "hsa-mir-1275" (miRBase Accession No. MI0006415, Sequence ID No. 247).

[0129] As used herein, the terms "hsa-miR-6779-5p gene" or "hsa-miR-6779-5p" include the hsa-miR-6779-5p gene (miRBase Accession No. MIMAT0027458) described in Sequence ID No. 46, as well as other species homologs or orthologs. The hsa-miR-6779-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6779-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6779" (miRBase Accession No. MI0022624, Sequence ID No. 248).

[0130] As used herein, the terms "hsa-miR-197-5p gene" or "hsa-miR-197-5p" include the hsa-miR-197-5p gene (miRBase Accession No. MIMAT0022691) described in Sequence ID No. 47, as well as other species homologs or orthologs. The hsa-miR-197-5p gene can be obtained by the method described by Lagos-Quintana M et al., 2003, RNA, Vol. 9, pp. 175-179. In addition, "hsa-miR-197-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-197" (miRBase Accession No. MI0000239, Sequence ID No. 249).

[0131] As used herein, the terms "hsa-miR-6845-5p gene" or "hsa-miR-6845-5p" include the hsa-miR-6845-5p gene (miRBase Accession No. MIMAT0027590) described in Sequence ID No. 48, as well as other species homologs or orthologs. The hsa-miR-6845-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6845-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6845" (miRBase Accession No. MI0022691, Sequence ID No. 250).

[0132] As used herein, the terms "hsa-miR-4327 gene" or "hsa-miR-4327" include the hsa-miR-4327 gene (miRBase Accession No. MIMAT0016889) described in Sequence ID No. 49, as well as other species homologs or orthologs. The hsa-miR-4327 gene can be obtained by the method described by Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, "hsa-miR-4327" is known to have a hairpin-like structure as its precursor, "hsa-mir-4327" (miRBase Accession No. MI0015867, Sequence ID No. 251).

[0133] As used herein, the terms "hsa-miR-4723-5p gene" or "hsa-miR-4723-5p" include the hsa-miR-4723-5p gene (miRBase Accession No. MIMAT0019838) described in Sequence ID No. 50, as well as other species homologs or orthologs. The hsa-miR-4723-5p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4723-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4723" (miRBase Accession No. MI0017359, Sequence ID No. 252).

[0134] As used herein, the terms "hsa-miR-4530 gene" or "hsa-miR-4530" include the hsa-miR-4530 gene (miRBase Accession No. MIMAT0019069) described in Sequence ID No. 51, as well as other species homologs or orthologs. The hsa-miR-4530 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4530" is known to have a hairpin-like structure as its precursor, "hsa-mir-4530" (miRBase Accession No. MI0016897, Sequence ID No. 253).

[0135] As used herein, the terms "hsa-miR-6771-5p gene" or "hsa-miR-6771-5p" include the hsa-miR-6771-5p gene (miRBase Accession No. MIMAT0027442) described in Sequence ID No. 52, as well as other species homologs or orthologs. The hsa-miR-6771-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6771-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6771" (miRBase Accession No. MI0022616, Sequence ID No. 254).

[0136] As used herein, the terms "hsa-miR-614 gene" or "hsa-miR-614" include the hsa-miR-614 gene (miRBase Accession No. MIMAT0003282) described in Sequence ID No. 53, as well as other species homologs or orthologs. The hsa-miR-614 gene can be obtained by the method described by Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. In addition, "hsa-miR-614" is known to have a hairpin-like structure as its precursor, "hsa-mir-614" (miRBase Accession No. MI0003627, Sequence ID No. 255).

[0137] As used herein, the terms "hsa-miR-92a-2-5p gene" or "hsa-miR-92a-2-5p" include the hsa-miR-92a-2-5p gene (miRBase Accession No. MIMAT0004508) described in Sequence ID No. 54, as well as other species homologs or orthologs. The hsa-miR-92a-2-5p gene can be obtained by the method described by Mourelatos Z et al., 2002, Genes Dev, Vol. 16, pp. 720-728. In addition, "hsa-miR-92a-2-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-92a-2" (miRBase Accession No. MI0000094, Sequence ID No. 256).

[0138] As used herein, the terms "hsa-miR-6891-5p gene" or "hsa-miR-6891-5p" include the hsa-miR-6891-5p gene (miRBase Accession No. MIMAT0027682) described in Sequence ID No. 55, as well as other species homologs or orthologs. The hsa-miR-6891-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6891-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6891" (miRBase Accession No. MI0022738, Sequence ID No. 257).

[0139] As used herein, the terms "hsa-miR-6124 gene" or "hsa-miR-6124" include the hsa-miR-6124 gene (miRBase Accession No. MIMAT0024597) described in Sequence ID No. 56, as well as other species homologs or orthologs. The hsa-miR-6124 gene can be obtained by the method described by Smith JL et al., 2012, J Virol, Vol. 86, pp. 5278-5287. In addition, "hsa-miR-6124" is known to have a hairpin-like structure as its precursor, "hsa-mir-6124" (miRBase Accession No. MI0021258, Sequence ID No. 258).

[0140] As used herein, the terms "hsa-miR-4687-3p gene" or "hsa-miR-4687-3p" include the hsa-miR-4687-3p gene (miRBase Accession No. MIMAT0019775) described in Sequence ID No. 57, as well as other species homologs or orthologs. The hsa-miR-4687-3p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4687-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4687" (miRBase Accession No. MI0017319, Sequence ID No. 259).

[0141] As used herein, the terms "hsa-miR-4442 gene" or "hsa-miR-4442" include the hsa-miR-4442 gene (miRBase Accession No. MIMAT0018960) described in Sequence ID No. 58, as well as other species homologs or orthologs. The hsa-miR-4442 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4442" is known to have a hairpin-like structure as its precursor, "hsa-mir-4442" (miRBase Accession No. MI0016785, Sequence ID No. 260).

[0142] As used herein, the terms "hsa-miR-7977 gene" or "hsa-miR-7977" include the hsa-miR-7977 gene (miRBase Accession No. MIMAT0031180) described in Sequence ID No. 59, as well as other species homologs or orthologs. The hsa-miR-7977 gene can be obtained by the method described by Velthut-Meikas A et al., 2013, Mol Endocrinol, online edition. In addition, "hsa-miR-7977" is known to have a hairpin-like structure as its precursor, "hsa-mir-7977" (miRBase Accession No. MI0025753, Sequence ID No. 261).

[0143] As used herein, the terms "hsa-miR-6785-5p gene" or "hsa-miR-6785-5p" include the hsa-miR-6785-5p gene (miRBase Accession No. MIMAT0027470) described in Sequence ID No. 60, as well as other species homologs or orthologs. The hsa-miR-6785-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6785-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6785" (miRBase Accession No. MI0022630, Sequence ID No. 262).

[0144] As used herein, the terms "hsa-miR-4497 gene" or "hsa-miR-4497" include the hsa-miR-4497 gene (miRBase Accession No. MIMAT0019032) described in Sequence ID No. 61, as well as other species homologs or orthologs. The hsa-miR-4497 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4497" is known to have a hairpin-like structure as its precursor, "hsa-mir-4497" (miRBase Accession No. MI0016859, Sequence ID No. 263).

[0145] As used herein, the terms "hsa-miR-8071 gene" or "hsa-miR-8071" include the hsa-miR-8071 gene described in Sequence ID No. 62 (miRBase Accession No. MIMAT0030998) and other species homologs or orthologs. The hsa-miR-8071 gene can be obtained by the method described by Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. In addition, "hsa-miR-8071" is known to have hairpin-like structures as its precursors, "hsa-mir-8071-1, hsa-mir-8071-2" (miRBase Accession No. MI0025907, MI0026417, Sequence IDs 264, 265).

[0146] As used herein, the terms "hsa-miR-663b gene" or "hsa-miR-663b" include the hsa-miR-663b gene (miRBase Accession No. MIMAT0005867) described in Sequence ID No. 63, as well as other species homologs or orthologs. The hsa-miR-663b gene can be obtained by the method described by Takada S et al., 2008, Leukemia, Vol. 22, pp. 1274-1278. In addition, "hsa-miR-663b" is known to have a hairpin-like structure as its precursor, "hsa-mir-663b" (miRBase Accession No. MI0006336, Sequence ID No. 266).

[0147] As used herein, the terms "hsa-miR-3180 gene" or "hsa-miR-3180" include the hsa-miR-3180 gene described in Sequence ID No. 64 (miRBase Accession No. MIMAT0018178) and other species homologs or orthologs. The hsa-miR-3180 gene can be obtained by the method described by Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. In addition, "hsa-miR-3180" is known to have hairpin-like structures as its precursors, "hsa-mir-3180-4, hsa-mir-3180-5" (miRBase Accession No. MI0016408, MI0016409, Sequence IDs 266, 268).

[0148] As used herein, the terms "hsa-miR-4251 gene" or "hsa-miR-4251" include the hsa-miR-4251 gene described in Sequence ID No. 65 (miRBase Accession No. MIMAT0016883) and other species homologs or orthologs. The hsa-miR-4251 gene can be obtained by the method described by Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, "hsa-miR-4251" is known to have a hairpin-like structure as its precursor, "hsa-mir-4251" (miRBase Accession No. MI0015861, Sequence ID No. 269).

[0149] As used herein, the terms "hsa-miR-1285-3p gene" or "hsa-miR-1285-3p" include the hsa-miR-1285-3p gene (miRBase Accession No. MIMAT0005876) described in Sequence ID No. 66, as well as other species homologs or orthologs. The hsa-miR-1285-3p gene can be obtained by the method described by Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. In addition, "hsa-miR-1285-3p" is known to have hairpin-like precursors, "hsa-mir-1285-1, hsa-mir-1285-2" (miRBase Accession No. MI0006346, MI0006347, Sequence ID No. 270, 271).

[0150] As used herein, the terms "hsa-miR-6870-5p gene" or "hsa-miR-6870-5p" include the hsa-miR-6870-5p gene (miRBase Accession No. MIMAT0027640) described in Sequence ID No. 67, as well as other species homologs or orthologs. The hsa-miR-6870-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6870-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6870" (miRBase Accession No. MI0022717, Sequence ID No. 272).

[0151] As used herein, the terms "hsa-miR-4484 gene" or "hsa-miR-4484" include the hsa-miR-4484 gene (miRBase Accession No. MIMAT0019018) described in Sequence ID No. 68, as well as other species homologs or orthologs. The hsa-miR-4484 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4484" is known to have a hairpin-like structure as its precursor, "hsa-mir-4484" (miRBase Accession No. MI0016845, Sequence ID No. 273).

[0152] As used herein, the terms "hsa-miR-4476 gene" or "hsa-miR-4476" include the hsa-miR-4476 gene (miRBase Accession No. MIMAT0019003) described in Sequence ID No. 69, as well as other species homologs or orthologs. The hsa-miR-4476 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4476" is known to have a hairpin-like structure as its precursor, "hsa-mir-4476" (miRBase Accession No. MI0016828, Sequence ID No. 274).

[0153] As used herein, the terms "hsa-miR-6749-5p gene" or "hsa-miR-6749-5p" include the hsa-miR-6749-5p gene (miRBase Accession No. MIMAT0027398) described in Sequence ID No. 70, as well as other species homologs or orthologs. The hsa-miR-6749-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6749-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6749" (miRBase Accession No. MI0022594, Sequence ID No. 275).

[0154] As used herein, the terms "hsa-miR-4454 gene" or "hsa-miR-4454" include the hsa-miR-4454 gene (miRBase Accession No. MIMAT0018976) described in Sequence ID No. 71, as well as other species homologs or orthologs. The hsa-miR-4454 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4454" is known to have a hairpin-like structure as its precursor, "hsa-mir-4454" (miRBase Accession No. MI0016800, Sequence ID No. 276).

[0155] As used herein, the terms "hsa-miR-6893-5p gene" or "hsa-miR-6893-5p" include the hsa-miR-6893-5p gene (miRBase Accession No. MIMAT0027686) described in Sequence ID No. 72, as well as other species homologs or orthologs. The hsa-miR-6893-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6893-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6893" (miRBase Accession No. MI0022740, Sequence ID No. 277).

[0156] As used herein, the terms "hsa-miR-6085 gene" or "hsa-miR-6085" include the hsa-miR-6085 gene (miRBase Accession No. MIMAT0023710) described in Sequence ID No. 73, as well as other species homologs or orthologs. The hsa-miR-6085 gene can be obtained by the method described by Voellenkle C et al., 2012, RNA, Vol. 18, pp. 472-484. In addition, "hsa-miR-6085" is known to have a hairpin-like structure as its precursor, "hsa-mir-6085" (miRBase Accession No. MI0020362, Sequence ID No. 278).

[0157] As used herein, the terms "hsa-miR-4787-5p gene" or "hsa-miR-4787-5p" include the hsa-miR-4787-5p gene (miRBase Accession No. MIMAT0019956) described in Sequence ID No. 74, as well as other species homologs or orthologs. The hsa-miR-4787-5p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4787-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4787" (miRBase Accession No. MI0017434, Sequence ID No. 279).

[0158] As used herein, the terms "hsa-miR-149-3p gene" or "hsa-miR-149-3p" include the hsa-miR-149-3p gene (miRBase Accession No. MIMAT0004609) described in Sequence ID No. 75, as well as other species homologs or orthologs. The hsa-miR-149-3p gene can be obtained by the method described by Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. In addition, "hsa-miR-149-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-149" (miRBase Accession No. MI0000478, Sequence ID No. 280).

[0159] As used herein, the terms "hsa-miR-7704 gene" or "hsa-miR-7704" include the hsa-miR-7704 gene (miRBase Accession No. MIMAT0030019) described in Sequence ID No. 76, as well as other species homologs or orthologs. The hsa-miR-7704 gene can be obtained by the method described by Swaminathan S et al., 2013, Biochem Biophys Res Commun, Vol. 434, pp. 228-234. In addition, "hsa-miR-7704" is known to have a hairpin-like structure as its precursor, "hsa-mir-7704" (miRBase Accession No. MI0025240, Sequence ID No. 281).

[0160] As used herein, the terms "hsa-miR-6125 gene" or "hsa-miR-6125" include the hsa-miR-6125 gene (miRBase Accession No. MIMAT0024598) described in Sequence ID No. 77, as well as other species homologs or orthologs. The hsa-miR-6125 gene can be obtained by the method described by Smith JL et al., 2012, J Virol, Vol. 86, pp. 5278-5287. In addition, "hsa-miR-6125" is known to have a hairpin-like structure as its precursor, "hsa-mir-6125" (miRBase Accession No. MI0021259, Sequence ID No. 282).

[0161] As used herein, the terms "hsa-miR-6090 gene" or "hsa-miR-6090" include the hsa-miR-6090 gene (miRBase Accession No. MIMAT0023715) described in Sequence ID No. 78, as well as other species homologs or orthologs. The hsa-miR-6090 gene can be obtained by the method described by Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. In addition, "hsa-miR-6090" is known to have a hairpin-like structure as its precursor, "hsa-mir-6090" (miRBase Accession No. MI0020367, Sequence ID No. 283).

[0162] As used herein, the terms "hsa-miR-3197 gene" or "hsa-miR-3197" include the hsa-miR-3197 gene (miRBase Accession No. MIMAT0015082) described in Sequence ID No. 79, as well as other species homologs or orthologs. The hsa-miR-3197 gene can be obtained by the method described by Stark MS et al., 2010, PLoS One, Vol. 5, e9685. In addition, "hsa-miR-3197" is known to have a hairpin-like structure as its precursor, "hsa-mir-3197" (miRBase Accession No. MI0014245, Sequence ID No. 284).

[0163] As used herein, the terms "hsa-miR-6850-5p gene" or "hsa-miR-6850-5p" include the hsa-miR-6850-5p gene (miRBase Accession No. MIMAT0027600) described in Sequence ID No. 80, as well as other species homologs or orthologs. The hsa-miR-6850-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6850-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6850" (miRBase Accession No. MI0022696, Sequence ID No. 285).

[0164] As used herein, the terms "hsa-miR-4467 gene" or "hsa-miR-4467" include the hsa-miR-4467 gene (miRBase Accession No. MIMAT0018994) described in Sequence ID No. 81, as well as other species homologs or orthologs. The hsa-miR-4467 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4467" is known to have a hairpin-like structure as its precursor, "hsa-mir-4467" (miRBase Accession No. MI0016818, Sequence ID No. 286).

[0165] As used herein, the terms "hsa-miR-6885-5p gene" or "hsa-miR-6885-5p" include the hsa-miR-6885-5p gene (miRBase Accession No. MIMAT0027670) described in Sequence ID No. 82, as well as other species homologs or orthologs. The hsa-miR-6885-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6885-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6885" (miRBase Accession No. MI0022732, Sequence ID No. 287).

[0166] As used herein, the terms "hsa-miR-6803-5p gene" or "hsa-miR-6803-5p" include the hsa-miR-6803-5p gene (miRBase Accession No. MIMAT0027506) described in Sequence ID No. 83, as well as other species homologs or orthologs. The hsa-miR-6803-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6803-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6803" (miRBase Accession No. MI0022648, Sequence ID No. 288).

[0167] As used herein, the terms "hsa-miR-6798-5p gene" or "hsa-miR-6798-5p" include the hsa-miR-6798-5p gene (miRBase Accession No. MIMAT0027496) described in Sequence ID No. 84, as well as other species homologs or orthologs. The hsa-miR-6798-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6798-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6798" (miRBase Accession No. MI0022643, Sequence ID No. 289).

[0168] As used herein, the terms "hsa-miR-6780b-5p gene" or "hsa-miR-6780b-5p" include the hsa-miR-6780b-5p gene (miRBase Accession No. MIMAT0027572) described in Sequence ID No. 85, as well as other species homologs or orthologs. The hsa-miR-6780b-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6780b-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6780b" (miRBase Accession No. MI0022681, Sequence ID No. 290).

[0169] As used herein, the terms "hsa-miR-6768-5p gene" or "hsa-miR-6768-5p" include the hsa-miR-6768-5p gene (miRBase Accession No. MIMAT0027436) described in Sequence ID No. 86, as well as other species homologs or orthologs. The hsa-miR-6768-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6768-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6768" (miRBase Accession No. MI0022613, Sequence ID No. 291).

[0170] As used herein, the terms "hsa-miR-5100 gene" or "hsa-miR-5100" include the hsa-miR-5100 gene (miRBase Accession No. MIMAT0022259) described in Sequence ID No. 87, as well as other species homologs or orthologs. The hsa-miR-5100 gene can be obtained by the method described by Tandon M et al., 2012, Oral Dis, Vol. 18, pp. 127-131. In addition, "hsa-miR-5100" is known to have a hairpin-like structure as its precursor, "hsa-mir-5100" (miRBase Accession No. MI0019116, Sequence ID No. 292).

[0171] As used herein, the terms “hsa-miR-6724-5p gene” or “hsa-miR-6724-5p” include the hsa-miR-6724-5p gene (miRBase Accession No. MIMAT0025856) described in Sequence ID No. 88, as well as other species homologs or orthologs. The hsa-miR-6724-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. Furthermore, "hsa-miR-6724-5p" is known to have hairpin-like precursors: "hsa-mir-6724-1, hsa-mir-6724-2, hsa-mir-6724-3, hsa-mir-6724-4" (miRBase Accession No. MI0022559, MI0031516, MI0031517, MI0031518, SEQ ID NOs. 293, 294, 295, 296).

[0172] As used herein, the terms "hsa-miR-6879-5p gene" or "hsa-miR-6879-5p" include the hsa-miR-6879-5p gene (miRBase Accession No. MIMAT0027658) described in Sequence ID No. 89, as well as other species homologs or orthologs. The hsa-miR-6879-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6879-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6879" (miRBase Accession No. MI0022726, Sequence ID No. 297).

[0173] As used herein, the terms "hsa-miR-7108-5p gene" or "hsa-miR-7108-5p" include the hsa-miR-7108-5p gene (miRBase Accession No. MIMAT0028113) described in Sequence ID No. 90, as well as other species homologs or orthologs. The hsa-miR-7108-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-7108" (miRBase Accession No. MI0022959, Sequence ID No. 298), which has a hairpin-like structure, is known as a precursor of "hsa-miR-7108-5p".

[0174] As used herein, the terms "hsa-miR-4649-5p gene" or "hsa-miR-4649-5p" include the hsa-miR-4649-5p gene (miRBase Accession No. MIMAT0019711) described in Sequence ID No. 91, as well as other species homologs or orthologs. The hsa-miR-4649-5p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4649-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4649" (miRBase Accession No. MI0017276, Sequence ID No. 299).

[0175] As used herein, the terms "hsa-miR-4739 gene" or "hsa-miR-4739" include the hsa-miR-4739 gene (miRBase Accession No. MIMAT0019868) described in Sequence ID No. 92, as well as other species homologs or orthologs. The hsa-miR-4739 gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4739" is known to have a hairpin-like structure as its precursor, "hsa-mir-4739" (miRBase Accession No. MI0017377, Sequence ID No. 300).

[0176] As used herein, the terms "hsa-miR-6089 gene" or "hsa-miR-6089" include the hsa-miR-6089 gene described in Sequence ID No. 93 (miRBase Accession No. MIMAT0023714) and other species homologs or orthologs. The hsa-miR-6089 gene can be obtained by the method described by Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. In addition, "hsa-miR-6089" is known to have hairpin-like precursors, "hsa-mir-6089-1, hsa-mir-6089-2" (miRBase Accession No. MI0020366, MI0023563, Sequence ID No. 301, 302).

[0177] As used herein, the terms "hsa-miR-1908-5p gene" or "hsa-miR-1908-5p" include the hsa-miR-1908-5p gene (miRBase Accession No. MIMAT0007881) described in Sequence ID No. 94, as well as other species homologs or orthologs. The hsa-miR-1908-5p gene can be obtained by the method described by Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. In addition, "hsa-miR-1908" is known to have a hairpin-like structure as its precursor, "hsa-mir-1908" (miRBase Accession No. MI0008329, Sequence ID No. 303).

[0178] As used herein, the terms "hsa-miR-4516 gene" or "hsa-miR-4516" include the hsa-miR-4516 gene (miRBase Accession No. MIMAT0019053) described in Sequence ID No. 95, as well as other species homologs or orthologs. The hsa-miR-4516 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4516" is known to have a hairpin-like structure as its precursor, "hsa-mir-4516" (miRBase Accession No. MI0016882, Sequence ID No. 304).

[0179] As used herein, the terms "hsa-miR-2861 gene" or "hsa-miR-2861" include the hsa-miR-2861 gene (miRBase Accession No. MIMAT0013802) described in Sequence ID No. 96, as well as other species homologs or orthologs. The hsa-miR-2861 gene can be obtained by the method described by Li H et al., 2009, J Clin Invest, Vol. 119, pp. 3666-3677. In addition, "hsa-miR-2861" is known to have a hairpin-like structure as its precursor, "hsa-mir-2861" (miRBase Accession No. MI0013006, Sequence ID No. 305).

[0180] As used herein, the terms "hsa-miR-4492 gene" or "hsa-miR-4492" include the hsa-miR-4492 gene (miRBase Accession No. MIMAT0019027) described in Sequence ID No. 97, as well as other species homologs or orthologs. The hsa-miR-4492 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4492" is known to have a hairpin-like structure as its precursor, "hsa-mir-4492" (miRBase Accession No. MI0016854, Sequence ID No. 306).

[0181] As used herein, the terms "hsa-miR-4294 gene" or "hsa-miR-4294" include the hsa-miR-4294 gene (miRBase Accession No. MIMAT0016849) described in Sequence ID No. 98, as well as other species homologs or orthologs. The hsa-miR-4294 gene can be obtained by the method described by Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, "hsa-miR-4294" is known to have a hairpin-like structure as its precursor, "hsa-mir-4294" (miRBase Accession No. MI0015827, Sequence ID No. 307).

[0182] As used herein, the terms "hsa-miR-6791-5p gene" or "hsa-miR-6791-5p" include the hsa-miR-6791-5p gene (miRBase Accession No. MIMAT0027482) described in Sequence ID No. 99, as well as other species homologs or orthologs. The hsa-miR-6791-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6791-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6791" (miRBase Accession No. MI0022636, Sequence ID No. 308).

[0183] As used herein, the terms "hsa-miR-1469 gene" or "hsa-miR-1469" include the hsa-miR-1469 gene (miRBase Accession No. MIMAT0007347) described in Sequence ID No. 100, as well as other species homologs or orthologs. The hsa-miR-1469 gene can be obtained by the method described by Kawaji H et al., 2008, BMC Genomics, Vol. 9, p. 157. In addition, "hsa-miR-1469" is known to have a hairpin-like structure as its precursor, "hsa-mir-1469" (miRBase Accession No. MI0007074, Sequence ID No. 309).

[0184] As used herein, the terms "hsa-miR-6752-5p gene" or "hsa-miR-6752-5p" include the hsa-miR-6752-5p gene (miRBase Accession No. MIMAT0027404) described in Sequence ID No. 101, as well as other species homologs or orthologs. The hsa-miR-6752-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6752-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6752" (miRBase Accession No. MI0022597, Sequence ID No. 310).

[0185] As used herein, the terms "hsa-miR-4730 gene" or "hsa-miR-4730" include the hsa-miR-4730 gene described in Sequence ID No. 102 (miRBase Accession No. MIMAT0019852) and other species homologs or orthologs. The hsa-miR-4730 gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4730" is known to have a hairpin-like structure as its precursor, "hsa-mir-4730" (miRBase Accession No. MI0017367, Sequence ID No. 311).

[0186] As used herein, the terms "hsa-miR-6126 gene" or "hsa-miR-6126" include the hsa-miR-6126 gene (miRBase Accession No. MIMAT0024599) described in Sequence ID No. 103, as well as other species homologs or orthologs. The hsa-miR-6126 gene can be obtained by the method described by Smith JL et al., 2012, J Virol, Vol. 86, pp. 5278-5287. In addition, "hsa-miR-6126" is known to have a hairpin-like structure as its precursor, "hsa-mir-6126" (miRBase Accession No. MI0021260, Sequence ID No. 312).

[0187] As used herein, the terms "hsa-miR-6869-5p gene" or "hsa-miR-6869-5p" include the hsa-miR-6869-5p gene (miRBase Accession No. MIMAT0027638) described in Sequence ID No. 104, as well as other species homologs or orthologs. The hsa-miR-6869-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6869-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6869" (miRBase Accession No. MI0022716, Sequence ID No. 313).

[0188] As used herein, the terms "hsa-miR-1268a gene" or "hsa-miR-1268a" include the hsa-miR-1268a gene (miRBase Accession No. MIMAT0005922) described in Sequence ID No. 105, as well as other species homologs or orthologs. The hsa-miR-1268a gene can be obtained by the method described by Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. In addition, "hsa-miR-1268a" is known to have a hairpin-like structure as its precursor, "hsa-mir-1268a" (miRBase Accession No. MI0006405, Sequence ID No. 314).

[0189] As used herein, the terms "hsa-miR-6799-5p gene" or "hsa-miR-6799-5p" include the hsa-miR-6799-5p gene (miRBase Accession No. MIMAT0027498) described in Sequence ID No. 106, as well as other species homologs or orthologs. The hsa-miR-6799-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6799-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6799" (miRBase Accession No. MI0022644, Sequence ID No. 315).

[0190] As used herein, the terms "hsa-miR-8069 gene" or "hsa-miR-8069" include the hsa-miR-8069 gene described in Sequence ID No. 107 (miRBase Accession No. MIMAT0030996) and other species homologs or orthologs. The hsa-miR-8069 gene can be obtained by the method described by Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. In addition, "hsa-miR-8069" is known to have hairpin-like precursors, "hsa-mir-8069-1, hsa-mir-8069-2" (miRBase Accession No. MI0025905, MI0031519, Sequence ID No. 316, 317).

[0191] As used herein, the terms "hsa-miR-3621 gene" or "hsa-miR-3621" include the hsa-miR-3621 gene (miRBase Accession No. MIMAT0018002) described in Sequence ID No. 108, as well as other species homologs or orthologs. The hsa-miR-3621 gene can be obtained by the method described by Witten D et al., 2010, BMC Biol, Vol. 8, p. 58. In addition, "hsa-miR-3621" is known to have a hairpin-like structure as its precursor, "hsa-mir-3621" (miRBase Accession No. MI0016012, Sequence ID No. 318).

[0192] As used herein, the terms "hsa-miR-4763-3p gene" or "hsa-miR-4763-3p" include the hsa-miR-4763-3p gene (miRBase Accession No. MIMAT0019913) described in Sequence ID No. 109, as well as other species homologs or orthologs. The hsa-miR-4763-3p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4763-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4763" (miRBase Accession No. MI0017404, Sequence ID No. 319).

[0193] As used herein, the terms "hsa-miR-1228-5p gene" or "hsa-miR-1228-5p" include the hsa-miR-1228-5p gene (miRBase Accession No. MIMAT0005582) described in Sequence ID No. 110, as well as other species homologs or orthologs. The hsa-miR-1228-5p gene can be obtained by the method described by Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. In addition, "hsa-miR-1228" (miRBase Accession No. MI0006318, Sequence ID No. 320), which has a hairpin-like structure, is known as a precursor of "hsa-miR-1228-5p".

[0194] As used herein, the terms "hsa-miR-760 gene" or "hsa-miR-760" include the hsa-miR-760 gene (miRBase Accession No. MIMAT0004957) described in Sequence ID No. 111, as well as other species homologs or orthologs. The hsa-miR-760 gene can be obtained by the method described by Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. In addition, "hsa-miR-760" is known to have a hairpin-like structure as its precursor, "hsa-mir-760" (miRBase Accession No. MI0005567, Sequence ID No. 321).

[0195] As used herein, the terms "hsa-miR-187-5p gene" or "hsa-miR-187-5p" include the hsa-miR-187-5p gene (miRBase Accession No. MIMAT0004561) described in Sequence ID No. 112, as well as other species homologs or orthologs. The hsa-miR-187-5p gene can be obtained by the method described by Lim LP et al., 2003, Science, Vol. 299, p. 1540. In addition, "hsa-miR-187-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-187" (miRBase Accession No. MI0000274, Sequence ID No. 322).

[0196] As used herein, the terms "hsa-miR-7111-5p gene" or "hsa-miR-7111-5p" include the hsa-miR-7111-5p gene (miRBase Accession No. MIMAT0028119) described in Sequence ID No. 113, as well as other species homologs or orthologs. The hsa-miR-7111-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-7111-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7111" (miRBase Accession No. MI0022962, Sequence ID No. 323).

[0197] As used herein, the terms "hsa-miR-6088 gene" or "hsa-miR-6088" include the hsa-miR-6088 gene (miRBase Accession No. MIMAT0023713) described in Sequence ID No. 114, as well as other species homologs or orthologs. The hsa-miR-6088 gene can be obtained by the method described by Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. In addition, "hsa-miR-6088" is known to have a hairpin-like structure as its precursor, "hsa-mir-6088" (miRBase Accession No. MI0020365, Sequence ID No. 324).

[0198] As used herein, the terms "hsa-miR-6805-3p gene" or "hsa-miR-6805-3p" include the hsa-miR-6805-3p gene (miRBase Accession No. MIMAT0027511) described in Sequence ID No. 115, as well as other species homologs or orthologs. The hsa-miR-6805-3p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6805-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6805" (miRBase Accession No. MI0022650, Sequence ID No. 325).

[0199] As used herein, the terms "hsa-miR-4640-5p gene" or "hsa-miR-4640-5p" include the hsa-miR-4640-5p gene (miRBase Accession No. MIMAT0019699) described in Sequence ID No. 116, as well as other species homologs or orthologs. The hsa-miR-4640-5p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4640-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4640" (miRBase Accession No. MI0017267, Sequence ID No. 326).

[0200] As used herein, the terms "hsa-miR-6721-5p gene" or "hsa-miR-6721-5p" include the hsa-miR-6721-5p gene (miRBase Accession No. MIMAT0025852) described in Sequence ID No. 117, as well as other species homologs or orthologs. The hsa-miR-6721-5p gene can be obtained by the method described by Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. In addition, "hsa-miR-6721-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6721" (miRBase Accession No. MI0022556, Sequence ID No. 327).

[0201] As used herein, the terms "hsa-miR-6880-5p gene" or "hsa-miR-6880-5p" include the hsa-miR-6880-5p gene (miRBase Accession No. MIMAT0027660) described in Sequence ID No. 118, as well as other species homologs or orthologs. The hsa-miR-6880-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6880-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6880" (miRBase Accession No. MI0022727, Sequence ID No. 328).

[0202] As used herein, the terms "hsa-miR-711 gene" or "hsa-miR-711" include the hsa-miR-711 gene (miRBase Accession No. MIMAT0012734) described in Sequence ID No. 119, as well as other species homologs or orthologs. The hsa-miR-711 gene can be obtained by the method described by Artzi S et al., 2008, BMC Bioinformatics, Vol. 9, p. 39. In addition, "hsa-miR-711" is known to have a hairpin-like structure as its precursor, "hsa-mir-711" (miRBase Accession No. MI0012488, Sequence ID No. 329).

[0203] As used herein, the terms "hsa-miR-128-1-5p gene" or "hsa-miR-128-1-5p" include the hsa-miR-128-1-5p gene (miRBase Accession No. MIMAT0026477) described in Sequence ID No. 120, as well as other species homologs or orthologs. The hsa-miR-128-1-5p gene can be obtained by the method described by Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. In addition, "hsa-miR-128-1" is known to have a hairpin-like structure as its precursor, "hsa-mir-128-1" (miRBase Accession No. MI0000447, Sequence ID No. 330).

[0204] As used herein, the terms "hsa-miR-4525 gene" or "hsa-miR-4525" include the hsa-miR-4525 gene (miRBase Accession No. MIMAT0019064) described in Sequence ID No. 121, as well as other species homologs or orthologs. The hsa-miR-4525 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4525" is known to have a hairpin-like structure as its precursor, "hsa-mir-4525" (miRBase Accession No. MI0016892, Sequence ID No. 331).

[0205] As used herein, the terms "hsa-miR-486-3p gene" or "hsa-miR-486-3p" include the hsa-miR-486-3p gene described in Sequence ID No. 122 (miRBase Accession No. MIMAT0004762) and other species homologs or orthologs. The hsa-miR-486-3p gene can be obtained by the method described by Fu H et al., 2005, FEBS Lett, Vol. 579, pp. 3849-3854. In addition, "hsa-miR-486-3p" is known to have hairpin-like precursors, "hsa-mir-486-1, hsa-mir-486-2" (miRBase Accession No. MI0002470, MI0023622, Sequence IDs 332, 333).

[0206] As used herein, the terms "hsa-miR-6756-5p gene" or "hsa-miR-6756-5p" include the hsa-miR-6756-5p gene (miRBase Accession No. MIMAT0027412) described in Sequence ID No. 123, as well as other species homologs or orthologs. The hsa-miR-6756-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6756-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6756" (miRBase Accession No. MI0022601, Sequence ID No. 334).

[0207] As used herein, the terms "hsa-miR-1260b gene" or "hsa-miR-1260b" include the hsa-miR-1260b gene (miRBase Accession No. MIMAT0015041) described in Sequence ID No. 124, as well as other species homologs or orthologs. The hsa-miR-1260b gene can be obtained by the method described by Stark MS et al., 2010, PLoS One, Vol. 5, e9685. In addition, "hsa-miR-1260b" is known to have a hairpin-like structure as its precursor, "hsa-mir-1260b" (miRBase Accession No. MI0014197, Sequence ID No. 335).

[0208] As used herein, the terms "hsa-miR-3184-5p gene" or "hsa-miR-3184-5p" include the hsa-miR-3184-5p gene (miRBase Accession No. MIMAT0015064) described in Sequence ID No. 125, as well as other species homologs or orthologs. The hsa-miR-3184-5p gene can be obtained by the method described by Stark MS et al., 2010, PLoS One, Vol. 5, e9685. In addition, "hsa-miR-3184-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3184" (miRBase Accession No. MI0014226, Sequence ID No. 336).

[0209] As used herein, the terms "hsa-miR-6075 gene" or "hsa-miR-6075" include the hsa-miR-6075 gene (miRBase Accession No. MIMAT0023700) described in Sequence ID No. 126, as well as other species homologs or orthologs. The hsa-miR-6075 gene can be obtained by the method described by Voellenkle C et al., 2012, RNA, Vol. 18, pp. 472-484. In addition, "hsa-miR-6075" is known to have a hairpin-like structure as its precursor, "hsa-mir-6075" (miRBase Accession No. MI0020352, Sequence ID No. 337).

[0210] As used herein, the terms "hsa-miR-204-3p gene" or "hsa-miR-204-3p" include the hsa-miR-204-3p gene (miRBase Accession No. MIMAT0022693) described in Sequence ID No. 127, as well as other species homologs or orthologs. The hsa-miR-204-3p gene can be obtained by the method described by Lim LP et al., 2003, Science, Vol. 299, p. 1540. In addition, "hsa-miR-204-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-204" (miRBase Accession No. MI0000284, Sequence ID No. 338).

[0211] As used herein, the terms "hsa-miR-4728-5p gene" or "hsa-miR-4728-5p" include the hsa-miR-4728-5p gene (miRBase Accession No. MIMAT0019849) described in Sequence ID No. 128, as well as other species homologs or orthologs. The hsa-miR-4728-5p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4728" is known to have a hairpin-like structure as its precursor, "hsa-mir-4728" (miRBase Accession No. MI0017365, Sequence ID No. 339).

[0212] As used herein, the terms "hsa-miR-4534 gene" or "hsa-miR-4534" include the hsa-miR-4534 gene (miRBase Accession No. MIMAT0019073) described in Sequence ID No. 129, as well as other species homologs or orthologs. The hsa-miR-4534 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4534" is known to have a hairpin-like structure as its precursor, "hsa-mir-4534" (miRBase Accession No. MI0016901, Sequence ID No. 340).

[0213] As used herein, the terms "hsa-miR-4758-5p gene" or "hsa-miR-4758-5p" include the hsa-miR-4758-5p gene (miRBase Accession No. MIMAT0019903) described in Sequence ID No. 130, as well as other species homologs or orthologs. The hsa-miR-4758-5p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4758-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4758" (miRBase Accession No. MI0017399, Sequence ID No. 341).

[0214] As used herein, the terms "hsa-miR-8063 gene" or "hsa-miR-8063" include the hsa-miR-8063 gene (miRBase Accession No. MIMAT0030990) described in Sequence ID No. 131, as well as other species homologs or orthologs. The hsa-miR-8063 gene can be obtained by the method described by Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. In addition, "hsa-miR-8063" is known to have a hairpin-like structure as its precursor, "hsa-mir-8063" (miRBase Accession No. MI0025899, Sequence ID No. 342).

[0215] As used herein, the terms "hsa-miR-6836-3p gene" or "hsa-miR-6836-3p" include the hsa-miR-6836-3p gene (miRBase Accession No. MIMAT0027575) described in Sequence ID No. 132, as well as other species homologs or orthologs. The hsa-miR-6836-3p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6836-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6836" (miRBase Accession No. MI0022682, Sequence ID No. 343).

[0216] As used herein, the terms "hsa-miR-6789-5p gene" or "hsa-miR-6789-5p" include the hsa-miR-6789-5p gene (miRBase Accession No. MIMAT0027478) described in Sequence ID No. 133, as well as other species homologs or orthologs. The hsa-miR-6789-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6789-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6789" (miRBase Accession No. MI0022634, Sequence ID No. 344).

[0217] As used herein, the terms "hsa-miR-744-5p gene" or "hsa-miR-744-5p" include the hsa-miR-744-5p gene (miRBase Accession No. MIMAT0004945) described in Sequence ID No. 134, as well as other species homologs or orthologs. The hsa-miR-744-5p gene can be obtained by the method described by Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. In addition, "hsa-miR-744-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-744" (miRBase Accession No. MI0005559, Sequence ID No. 345).

[0218] As used herein, the terms "hsa-miR-1909-3p gene" or "hsa-miR-1909-3p" include the hsa-miR-1909-3p gene (miRBase Accession No. MIMAT0007883) described in Sequence ID No. 135, as well as other species homologs or orthologs. The hsa-miR-1909-3p gene can be obtained by the method described by Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. In addition, "hsa-miR-1909-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1909" (miRBase Accession No. MI0008330, Sequence ID No. 346).

[0219] As used herein, the terms "hsa-miR-887-3p gene" or "hsa-miR-887-3p" include the hsa-miR-887-3p gene (miRBase Accession No. MIMAT0004951) described in Sequence ID No. 136, as well as other species homologs or orthologs. The hsa-miR-887-3p gene can be obtained by the method described by Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. In addition, "hsa-miR-887-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-887" (miRBase Accession No. MI0005562, Sequence ID No. 347).

[0220] As used herein, the terms "hsa-miR-4745-5p gene" or "hsa-miR-4745-5p" include the hsa-miR-4745-5p gene (miRBase Accession No. MIMAT0019878) described in Sequence ID No. 137, as well as other species homologs or orthologs. The hsa-miR-4745-5p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4745-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4745" (miRBase Accession No. MI0017384, Sequence ID No. 348).

[0221] As used herein, the terms "hsa-miR-4433a-3p gene" or "hsa-miR-4433a-3p" include the hsa-miR-4433a-3p gene (miRBase Accession No. MIMAT0018949) described in Sequence ID No. 138, as well as other species homologs or orthologs. The hsa-miR-4433a-3p gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4433a-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4433a" (miRBase Accession No. MI0016773, Sequence ID No. 349).

[0222] As used herein, the terms "hsa-miR-5090 gene" or "hsa-miR-5090" include the hsa-miR-5090 gene (miRBase Accession No. MIMAT0021082) described in Sequence ID No. 139, as well as other species homologs or orthologs. The hsa-miR-5090 gene can be obtained by the method described by Ding N et al., 2011, J Radiat Res, Vol. 52, pp. 425-432. In addition, "hsa-miR-5090" is known to have a hairpin-like structure as its precursor, "hsa-mir-5090" (miRBase Accession No. MI0017979, Sequence ID No. 350).

[0223] As used herein, the terms "hsa-miR-296-5p gene" or "hsa-miR-296-5p" include the hsa-miR-296-5p gene (miRBase Accession No. MIMAT0000690) described in Sequence ID No. 140, as well as other species homologs or orthologs. The hsa-miR-296-5p gene can be obtained by the method described by Houbaviy HB et al., 2003, Dev Cell, Vol. 5, pp. 351-358. In addition, "hsa-miR-296-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-296" (miRBase Accession No. MI0000747, Sequence ID No. 351).

[0224] As used herein, the terms "hsa-miR-939-5p gene" or "hsa-miR-939-5p" include the hsa-miR-939-5p gene (miRBase Accession No. MIMAT0004982) described in Sequence ID No. 141, as well as other species homologs or orthologs. The hsa-miR-939-5p gene can be obtained by the method described by Lui WO et al., 2007, Cancer Res, Vol. 67, pp. 6031-6043. In addition, "hsa-miR-939-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-939" (miRBase Accession No. MI0005761, Sequence ID No. 352).

[0225] As used herein, the terms "hsa-miR-3648 gene" or "hsa-miR-3648" include the hsa-miR-3648 gene (miRBase Accession No. MIMAT0018068) described in Sequence ID No. 142, as well as other species homologs or orthologs. The hsa-miR-3648 gene can be obtained by the method described by Meiri E et al., 2010, Nucleic Acids Res, Vol. 38, pp. 6234-6246. In addition, "hsa-miR-3648" is known to have hairpin-like precursors, "hsa-mir-3648-1, hsa-mir-3648-2" (miRBase Accession No. MI0016048, MI0031512, Sequence ID No. 353, 354).

[0226] As used herein, the terms "hsa-miR-3196 gene" or "hsa-miR-3196" include the hsa-miR-3196 gene (miRBase Accession No. MIMAT0015080) described in Sequence ID No. 143, as well as other species homologs or orthologs. The hsa-miR-3196 gene can be obtained by the method described by Stark MS et al., 2010, PLoS One, Vol. 5, e9685. In addition, "hsa-miR-3196" is known to have a hairpin-like structure as its precursor, "hsa-mir-3196" (miRBase Accession No. MI0014241, Sequence ID No. 355).

[0227] As used herein, the terms "hsa-miR-6722-3p gene" or "hsa-miR-6722-3p" include the hsa-miR-6722-3p gene (miRBase Accession No. MIMAT0025854) described in Sequence ID No. 144, as well as other species homologs or orthologs. The hsa-miR-6722-3p gene can be obtained by the method described by Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. In addition, "hsa-miR-6722-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6722" (miRBase Accession No. MI0022557, Sequence ID No. 356).

[0228] As used herein, the terms "hsa-miR-6805-5p gene" or "hsa-miR-6805-5p" include the hsa-miR-6805-5p gene (miRBase Accession No. MIMAT0027510) described in Sequence ID No. 145, as well as other species homologs or orthologs. The hsa-miR-6805-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6805-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6805" (miRBase Accession No. MI0022650, Sequence ID No. 325).

[0229] As used herein, the terms "hsa-miR-1202 gene" or "hsa-miR-1202" include the hsa-miR-1202 gene (miRBase Accession No. MIMAT0005865) described in Sequence ID No. 146, as well as other species homologs or orthologs. The hsa-miR-1202 gene can be obtained by the method described by Marton S et al., 2008, Leukemia, Vol. 22, pp. 330-338. In addition, "hsa-miR-1202" is known to have a hairpin-like structure as its precursor, "hsa-mir-1202" (miRBase Accession No. MI0006334, Sequence ID No. 357).

[0230] As used herein, the terms "hsa-miR-6775-5p gene" or "hsa-miR-6775-5p" include the hsa-miR-6775-5p gene (miRBase Accession No. MIMAT0027450) described in Sequence ID No. 147, as well as other species homologs or orthologs. The hsa-miR-6775-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6775-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6775" (miRBase Accession No. MI0022620, Sequence ID No. 358).

[0231] As used herein, the terms "hsa-miR-6087 gene" or "hsa-miR-6087" include the hsa-miR-6087 gene (miRBase Accession No. MIMAT0023712) described in Sequence ID No. 148, as well as other species homologs or orthologs. The hsa-miR-6087 gene can be obtained by the method described by Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. In addition, "hsa-miR-6087" is known to have a hairpin-like structure as its precursor, "hsa-mir-6087" (miRBase Accession No. MI0020364, Sequence ID No. 359).

[0232] As used herein, the terms "hsa-miR-6765-5p gene" or "hsa-miR-6765-5p" include the hsa-miR-6765-5p gene (miRBase Accession No. MIMAT0027430) described in Sequence ID No. 149, as well as other species homologs or orthologs. The hsa-miR-6765-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6765-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6765" (miRBase Accession No. MI0022610, Sequence ID No. 360).

[0233] As used herein, the terms "hsa-miR-6875-5p gene" or "hsa-miR-6875-5p" include the hsa-miR-6875-5p gene (miRBase Accession No. MIMAT0027650) described in Sequence ID No. 150, as well as other species homologs or orthologs. The hsa-miR-6875-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6875-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6875" (miRBase Accession No. MI0022722, Sequence ID No. 361).

[0234] As used herein, the terms "hsa-miR-4674 gene" or "hsa-miR-4674" include the hsa-miR-4674 gene (miRBase Accession No. MIMAT0019756) described in Sequence ID No. 151, as well as other species homologs or orthologs. The hsa-miR-4674 gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4674" is known to have a hairpin-like structure as its precursor, "hsa-mir-4674" (miRBase Accession No. MI0017305, Sequence ID No. 362).

[0235] As used herein, the terms "hsa-miR-1233-5p gene" or "hsa-miR-1233-5p" include the hsa-miR-1233-5p gene described in Sequence ID No. 152 (miRBase Accession No. MIMAT0022943) and other species homologs or orthologs. The hsa-miR-1233-5p gene can be obtained by the method described by Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. In addition, "hsa-miR-1233-5p" is known to have hairpin-like precursors, "hsa-mir-1233-1, hsa-mir-1233-2" (miRBase Accession No. MI0006323, MI0015973, Sequence ID No. 363, 364).

[0236] As used herein, the terms "hsa-miR-7114-5p gene" or "hsa-miR-7114-5p" include the hsa-miR-7114-5p gene (miRBase Accession No. MIMAT0028125) described in Sequence ID No. 153, as well as other species homologs or orthologs. The hsa-miR-7114-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-7114-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7114" (miRBase Accession No. MI0022965, Sequence ID No. 365).

[0237] As used herein, the terms "hsa-miR-5787 gene" or "hsa-miR-5787" include the hsa-miR-5787 gene (miRBase Accession No. MIMAT0023252) described in Sequence ID No. 154, as well as other species homologs or orthologs. The hsa-miR-5787 gene can be obtained by the method described by Yoo H et al., 2011, Biochem Biophys Res Commun, Vol. 415, pp. 567-572. In addition, "hsa-miR-5787" is known to have a hairpin-like structure as its precursor, "hsa-mir-5787" (miRBase Accession No. MI0019797, Sequence ID No. 366).

[0238] As used herein, the terms "hsa-miR-8072 gene" or "hsa-miR-8072" include the hsa-miR-8072 gene (miRBase Accession No. MIMAT0030999) described in Sequence ID No. 155, as well as other species homologs or orthologs. The hsa-miR-8072 gene can be obtained by the method described by Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. In addition, "hsa-miR-8072" is known to have a hairpin-like structure as its precursor, "hsa-mir-8072" (miRBase Accession No. MI0025908, Sequence ID No. 367).

[0239] As used herein, the terms "hsa-miR-3619-3p gene" or "hsa-miR-3619-3p" include the hsa-miR-3619-3p gene (miRBase Accession No. MIMAT0019219) described in Sequence ID No. 156, as well as other species homologs or orthologs. The hsa-miR-3619-3p gene can be obtained by the method described by Witten D et al., 2010, BMC Biol, Vol. 8, p. 58. In addition, "hsa-miR-3619-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3619" (miRBase Accession No. MI0016009, Sequence ID No. 368).

[0240] As used herein, the terms "hsa-miR-4632-5p gene" or "hsa-miR-4632-5p" include the hsa-miR-4632-5p gene (miRBase Accession No. MIMAT0022977) described in Sequence ID No. 157, as well as other species homologs or orthologs. The hsa-miR-4632-5p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4632-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4632" (miRBase Accession No. MI0017259, Sequence ID No. 369).

[0241] As used herein, the terms "hsa-miR-6800-5p gene" or "hsa-miR-6800-5p" include the hsa-miR-6800-5p gene (miRBase Accession No. MIMAT0027500) described in Sequence ID No. 158, as well as other species homologs or orthologs. The hsa-miR-6800-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6800-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6800" (miRBase Accession No. MI0022645, Sequence ID No. 370).

[0242] As used herein, the terms "hsa-miR-4634 gene" or "hsa-miR-4634" include the hsa-miR-4634 gene (miRBase Accession No. MIMAT0019691) described in Sequence ID No. 159, as well as other species homologs or orthologs. The hsa-miR-4634 gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4634" is known to have a hairpin-like structure as its precursor, "hsa-mir-4634" (miRBase Accession No. MI0017261, Sequence ID No. 371).

[0243] As used herein, the terms "hsa-miR-4486 gene" or "hsa-miR-4486" include the hsa-miR-4486 gene (miRBase Accession No. MIMAT0019020) described in Sequence ID No. 160, as well as other species homologs or orthologs. The hsa-miR-4486 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4486" is known to have a hairpin-like structure as its precursor, "hsa-mir-4486" (miRBase Accession No. MI0016847, Sequence ID No. 372).

[0244] As used herein, the terms "hsa-miR-6727-5p gene" or "hsa-miR-6727-5p" include the hsa-miR-6727-5p gene (miRBase Accession No. MIMAT0027355) described in Sequence ID No. 161, as well as other species homologs or orthologs. The hsa-miR-6727-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6727-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6727" (miRBase Accession No. MI0022572, Sequence ID No. 373).

[0245] As used herein, the terms "hsa-miR-4505 gene" or "hsa-miR-4505" include the hsa-miR-4505 gene (miRBase Accession No. MIMAT0019041) described in Sequence ID No. 162, as well as other species homologs or orthologs. The hsa-miR-4505 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4505" is known to have a hairpin-like structure as its precursor, "hsa-mir-4505" (miRBase Accession No. MI0016868, Sequence ID No. 374).

[0246] As used herein, the terms "hsa-miR-4725-3p gene" or "hsa-miR-4725-3p" include the hsa-miR-4725-3p gene (miRBase Accession No. MIMAT0019844) described in Sequence ID No. 163, as well as other species homologs or orthologs. The hsa-miR-4725-3p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4725-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4725" (miRBase Accession No. MI0017362, Sequence ID No. 375).

[0247] As used herein, the terms "hsa-miR-1538 gene" or "hsa-miR-1538" include the hsa-miR-1538 gene (miRBase Accession No. MIMAT0007400) described in Sequence ID No. 164, as well as other species homologs or orthologs. The hsa-miR-1538 gene can be obtained by the method described by Azuma-Mukai A et al., 2008, Proc Natl Acad Sci USA, Vol. 105, pp. 7964-7969. In addition, "hsa-miR-1538" is known to have a hairpin-like structure as its precursor, "hsa-mir-1538" (miRBase Accession No. MI0007259, Sequence ID No. 376).

[0248] As used herein, the terms "hsa-miR-320b gene" or "hsa-miR-320b" include the hsa-miR-320b gene (miRBase Accession No. MIMAT0005792) described in Sequence ID No. 165, as well as other species homologs or orthologs. The hsa-miR-320b gene can be obtained by the method described by Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. In addition, "hsa-miR-320b" is known to have hairpin-like structures as its precursors, "hsa-mir-320b-1, hsa-mir-320b-2" (miRBase Accession No. MI0003776, MI0003839, Sequence ID No. 377, 378).

[0249] As used herein, the terms "hsa-miR-1915-5p gene" or "hsa-miR-1915-5p" include the hsa-miR-1915-5p gene (miRBase Accession No. MIMAT0007891) described in Sequence ID No. 166, as well as other species homologs or orthologs. The hsa-miR-1915-5p gene can be obtained by the method described by Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. In addition, "hsa-miR-1915-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1915" (miRBase Accession No. MI0008336, Sequence ID No. 379).

[0250] As used herein, the terms "hsa-miR-328-5p gene" or "hsa-miR-328-5p" include the hsa-miR-328-5p gene (miRBase Accession No. MIMAT0026486) described in Sequence ID No. 167, as well as other species homologs or orthologs. The hsa-miR-328-5p gene can be obtained by the method described by Kim J et al., 2004, Proc Natl Acad Sci USA, Vol. 101, pp. 360-365. Furthermore, "hsa-miR-328-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-328" (miRBase Accession No. MI0000804, Sequence ID No. 380).

[0251] As used herein, the terms "hsa-miR-6820-5p gene" or "hsa-miR-6820-5p" include the hsa-miR-6820-5p gene (miRBase Accession No. MIMAT0027540) described in Sequence ID No. 168, as well as other species homologs or orthologs. The hsa-miR-6820-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6820-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6820" (miRBase Accession No. MI0022665, Sequence ID No. 381).

[0252] As used herein, the terms "hsa-miR-6726-5p gene" or "hsa-miR-6726-5p" include the hsa-miR-6726-5p gene (miRBase Accession No. MIMAT0027353) described in Sequence ID No. 169, as well as other species homologs or orthologs. The hsa-miR-6726-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6726" (miRBase Accession No. MI0022571, Sequence ID No. 382), which has a hairpin-like structure, is known as a precursor of "hsa-miR-6726-5p".

[0253] As used herein, the terms "hsa-miR-3665 gene" or "hsa-miR-3665" include the hsa-miR-3665 gene (miRBase Accession No. MIMAT0018087) described in Sequence ID No. 170, as well as other species homologs or orthologs. The hsa-miR-3665 gene can be obtained by the method described by Xie X et al., 2005, Nature, Vol. 434, pp. 338-345. In addition, "hsa-miR-3665" is known to have a hairpin-like structure as its precursor, "hsa-mir-3665" (miRBase Accession No. MI0016066, Sequence ID No. 383).

[0254] As used herein, the terms "hsa-miR-638 gene" or "hsa-miR-638" include the hsa-miR-638 gene (miRBase Accession No. MIMAT0003308) described in Sequence ID No. 171, as well as other species homologs or orthologs. The hsa-miR-638 gene can be obtained by the method described by Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. In addition, "hsa-miR-638" is known to have a hairpin-like structure as its precursor, "hsa-mir-638" (miRBase Accession No. MI0003653, Sequence ID No. 384).

[0255] As used herein, the terms "hsa-miR-762 gene" or "hsa-miR-762" include the hsa-miR-762 gene described in Sequence ID No. 172 (miRBase Accession No. MIMAT0010313) and other species homologs or orthologs. The hsa-miR-762 gene can be obtained by the method described by Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. In addition, "hsa-miR-762" is known to have a hairpin-like structure as its precursor, "hsa-mir-762" (miRBase Accession No. MI0003892, Sequence ID No. 385).

[0256] As used herein, the terms "hsa-miR-4466 gene" or "hsa-miR-4466" include the hsa-miR-4466 gene (miRBase Accession No. MIMAT0018993) described in Sequence ID No. 173, as well as other species homologs or orthologs. The hsa-miR-4466 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4466" is known to have a hairpin-like structure as its precursor, "hsa-mir-4466" (miRBase Accession No. MI0016817, Sequence ID No. 386).

[0257] As used herein, the terms "hsa-miR-3940-5p gene" or "hsa-miR-3940-5p" include the hsa-miR-3940-5p gene (miRBase Accession No. MIMAT0019229) described in Sequence ID No. 174, as well as other species homologs or orthologs. The hsa-miR-3940-5p gene can be obtained by the method described by Liao JY et al., 2010, PLoS One, Vol. 5, e10563. In addition, "hsa-miR-3940-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3940" (miRBase Accession No. MI0016597, Sequence ID No. 387).

[0258] As used herein, the terms "hsa-miR-1237-5p gene" or "hsa-miR-1237-5p" include the hsa-miR-1237-5p gene (miRBase Accession No. MIMAT0022946) described in Sequence ID No. 175, as well as other species homologs or orthologs. The hsa-miR-1237-5p gene can be obtained by the method described by Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. In addition, "hsa-miR-1237-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1237" (miRBase Accession No. MI0006327, Sequence ID No. 388).

[0259] As used herein, the terms "hsa-miR-575 gene" or "hsa-miR-575" include the hsa-miR-575 gene described in Sequence ID No. 176 (miRBase Accession No. MIMAT0003240) and other species homologs or orthologs. The hsa-miR-575 gene can be obtained by the method described by Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. In addition, "hsa-miR-575" is known to have a hairpin-like structure as its precursor, "hsa-mir-575" (miRBase Accession No. MI0003582, Sequence ID No. 389).

[0260] As used herein, the terms "hsa-miR-3656 gene" or "hsa-miR-3656" include the hsa-miR-3656 gene (miRBase Accession No. MIMAT0018076) described in Sequence ID No. 177, as well as other species homologs or orthologs. The hsa-miR-3656 gene can be obtained by the method described by Meiri E et al., 2010, Nucleic Acids Res, Vol. 38, pp. 6234-6246. In addition, "hsa-miR-3656" is known to have a hairpin-like structure as its precursor, "hsa-mir-3656" (miRBase Accession No. MI0016056, Sequence ID No. 390).

[0261] As used herein, the terms "hsa-miR-4488 gene" or "hsa-miR-4488" include the hsa-miR-4488 gene (miRBase Accession No. MIMAT0019022) described in Sequence ID No. 178, as well as other species homologs or orthologs. The hsa-miR-4488 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4488" is known to have a hairpin-like structure as its precursor, "hsa-mir-4488" (miRBase Accession No. MI0016849, Sequence ID No. 391).

[0262] As used herein, the terms "hsa-miR-4281 gene" or "hsa-miR-4281" include the hsa-miR-4281 gene (miRBase Accession No. MIMAT0016907) described in Sequence ID No. 179, as well as other species homologs or orthologs. The hsa-miR-4281 gene can be obtained by the method described by Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, "hsa-miR-4281" is known to have a hairpin-like structure as its precursor, "hsa-mir-4281" (miRBase Accession No. MI0015885, Sequence ID No. 392).

[0263] As used herein, the terms "hsa-miR-6781-5p gene" or "hsa-miR-6781-5p" include the hsa-miR-6781-5p gene (miRBase Accession No. MIMAT0027462) described in Sequence ID No. 180, as well as other species homologs or orthologs. The hsa-miR-6781-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6781-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6781" (miRBase Accession No. MI0022626, Sequence ID No. 393).

[0264] As used herein, the terms "hsa-miR-4532 gene" or "hsa-miR-4532" include the hsa-miR-4532 gene (miRBase Accession No. MIMAT0019071) described in Sequence ID No. 181, as well as other species homologs or orthologs. The hsa-miR-4532 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4532" is known to have a hairpin-like structure as its precursor, "hsa-mir-4532" (miRBase Accession No. MI0016899, Sequence ID No. 394).

[0265] As used herein, the terms "hsa-miR-4665-5p gene" or "hsa-miR-4665-5p" include the hsa-miR-4665-5p gene (miRBase Accession No. MIMAT0019739) described in Sequence ID No. 182, as well as other species homologs or orthologs. The hsa-miR-4665-5p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4665-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4665" (miRBase Accession No. MI0017295, Sequence ID No. 395).

[0266] As used herein, the terms "hsa-miR-6816-5p gene" or "hsa-miR-6816-5p" include the hsa-miR-6816-5p gene (miRBase Accession No. MIMAT0027532) described in Sequence ID No. 183, as well as other species homologs or orthologs. The hsa-miR-6816-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6816-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6816" (miRBase Accession No. MI0022661, Sequence ID No. 396).

[0267] As used herein, the term "hsa-miR-4508 gene" or "hsa-miR-4508" includes the hsa-miR-4508 gene described in SEQ ID NO: 184 (miRBase Accession No. MIMAT0019045), as well as homologs or orthologs of other species. The hsa-miR-4508 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-miR-4508" is known to have a hairpin-like structure as its precursor, "hsa-mir-4508" (miRBase Accession No. MI0016872, SEQ ID NO: 397).

[0268] As used herein, the term "hsa-miR-6784-5p gene" or "hsa-miR-6784-5p" includes the hsa-miR-6784-5p gene described in SEQ ID NO: 185 (miRBase Accession No. MIMAT0027468), as well as homologs or orthologs of other species. The hsa-miR-6784-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645. Also, "hsa-miR-6784-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6784" (miRBase Accession No. MI0022629, SEQ ID NO: 398).

[0269] As used herein, the term "hsa-miR-6786-5p gene" or "hsa-miR-6786-5p" includes the hsa-miR-6786-5p gene described in SEQ ID NO: 186 (miRBase Accession No. MIMAT0027472), homologs or orthologs of other species, etc. The hsa-miR-6786-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6786-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6786" (miRBase Accession No. MI0022631, SEQ ID NO: 399).

[0270] As used herein, the term "hsa-miR-4741 gene" or "hsa-miR-4741" includes the hsa-miR-4741 gene described in SEQ ID NO: 187 (miRBase Accession No. MIMAT0019871), homologs or orthologs of other species, etc. The hsa-miR-4741 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4741" is known to have a hairpin-like structure as its precursor, "hsa-mir-4741" (miRBase Accession No. MI0017379, SEQ ID NO: 400).

[0271] As used herein, the terms "hsa-miR-1343-5p gene" or "hsa-miR-1343-5p" include the hsa-miR-1343-5p gene (miRBase Accession No. MIMAT0027038) described in Sequence ID No. 188, as well as other species homologs or orthologs. The hsa-miR-1343-5p gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-1343-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1343" (miRBase Accession No. MI0017320, Sequence ID No. 401).

[0272] As used herein, the terms "hsa-miR-1227-5p gene" or "hsa-miR-1227-5p" include the hsa-miR-1227-5p gene (miRBase Accession No. MIMAT0022941) described in Sequence ID No. 189, as well as other species homologs or orthologs. The hsa-miR-1227-5p gene can be obtained by the method described by Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. In addition, "hsa-miR-1227-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1227" (miRBase Accession No. MI0006316, Sequence ID No. 402).

[0273] As used herein, the terms "hsa-miR-4734 gene" or "hsa-miR-4734" include the hsa-miR-4734 gene (miRBase Accession No. MIMAT0019859) described in Sequence ID No. 190, as well as other species homologs or orthologs. The hsa-miR-4734 gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4734" is known to have a hairpin-like structure as its precursor, "hsa-mir-4734" (miRBase Accession No. MI0017371, Sequence ID No. 403).

[0274] As used herein, the terms "hsa-miR-3960 gene" or "hsa-miR-3960" include the hsa-miR-3960 gene (miRBase Accession No. MIMAT0019337) described in Sequence ID No. 191, as well as other species homologs or orthologs. The hsa-miR-3960 gene can be obtained by the method described by Hu R et al., 2011, J Biol Chem, Vol. 286, pp. 12328-12339. In addition, "hsa-miR-3960" is known to have a hairpin-like structure as its precursor, "hsa-mir-3960" (miRBase Accession No. MI0016964, Sequence ID No. 404).

[0275] As used herein, the terms "hsa-miR-128-2-5p gene" or "hsa-miR-128-2-5p" include the hsa-miR-128-2-5p gene (miRBase Accession No. MIMAT0031095) described in Sequence ID No. 192, as well as other species homologs or orthologs. The hsa-miR-128-2-5p gene can be obtained by the method described by Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. In addition, "hsa-miR-128-2-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-128-2" (miRBase Accession No. MI0000727, Sequence ID No. 405).

[0276] As used herein, the terms "hsa-miR-6743-5p gene" or "hsa-miR-6743-5p" include the hsa-miR-6743-5p gene (miRBase Accession No. MIMAT0027387) described in Sequence ID No. 193, as well as other species homologs or orthologs. The hsa-miR-6743-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6743-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6743" (miRBase Accession No. MI0022588, Sequence ID No. 406).

[0277] As used herein, the terms "hsa-miR-663a gene" or "hsa-miR-663a" include the hsa-miR-663a gene (miRBase Accession No. MIMAT0003326) described in Sequence ID No. 194, as well as other species homologs or orthologs. The hsa-miR-663a gene can be obtained by the method described by Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. In addition, "hsa-miR-663a" is known to have a hairpin-like structure as its precursor, "hsa-mir-663a" (miRBase Accession No. MI0003672, Sequence ID No. 407).

[0278] As used herein, the terms "hsa-miR-6729-5p gene" or "hsa-miR-6729-5p" include the hsa-miR-6729-5p gene (miRBase Accession No. MIMAT0027359) described in Sequence ID No. 195, as well as other species homologs or orthologs. The hsa-miR-6729-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. In addition, "hsa-miR-6729-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6729" (miRBase Accession No. MI0022574, Sequence ID No. 408).

[0279] As used herein, the terms "hsa-miR-1915-3p gene" or "hsa-miR-1915-3p" include the hsa-miR-1915-3p gene (miRBase Accession No. MIMAT0007892) described in Sequence ID No. 196, as well as other species homologs or orthologs. The hsa-miR-1915-3p gene can be obtained by the method described by Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. In addition, "hsa-miR-1915-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1915" (miRBase Accession No. MI0008336, Sequence ID No. 379).

[0280] As used herein, the terms "hsa-miR-1268b gene" or "hsa-miR-1268b" include the hsa-miR-1268b gene (miRBase Accession No. MIMAT0018925) described in Sequence ID No. 197, as well as other species homologs or orthologs. The hsa-miR-1268b gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-1268b" is known to have a hairpin-like structure as its precursor, "hsa-mir-1268b" (miRBase Accession No. MI0016748, Sequence ID No. 409).

[0281] As used herein, the terms "hsa-miR-4651 gene" or "hsa-miR-4651" include the hsa-miR-4651 gene (miRBase Accession No. MIMAT0019715) described in Sequence ID No. 198, as well as other species homologs or orthologs. The hsa-miR-4651 gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, "hsa-miR-4651" is known to have a hairpin-like structure as its precursor, "hsa-mir-4651" (miRBase Accession No. MI0017279, Sequence ID No. 410).

[0282] As used herein, the terms "hsa-miR-3178 gene" or "hsa-miR-3178" include the hsa-miR-3178 gene (miRBase Accession No. MIMAT0015055) described in Sequence ID No. 199, as well as other species homologs or orthologs. The hsa-miR-3178 gene can be obtained by the method described by Stark MS et al., 2010, PLoS One, Vol. 5, e9685. In addition, "hsa-miR-3178" is known to have a hairpin-like structure as its precursor, "hsa-mir-3178" (miRBase Accession No. MI0014212, Sequence ID No. 411).

[0283] As used herein, the terms "hsa-miR-4463 gene" or "hsa-miR-4463" include the hsa-miR-4463 gene (miRBase Accession No. MIMAT0018987) described in Sequence ID No. 200, as well as other species homologs or orthologs. The hsa-miR-4463 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, "hsa-miR-4463" is known to have a hairpin-like structure as its precursor, "hsa-mir-4463" (miRBase Accession No. MI0016811, Sequence ID No. 412).

[0284] When mature miRNAs are excised from hairpin-like RNA precursors, one to several bases may be shortened or lengthened at the beginning or end of the sequence, or base substitutions may occur, resulting in mutants, which are called isomiRs (Morin RD. et al., 2008, Genome Res., Vol. 18, pp. 610-621). miRBase (version 21) shows not only the nucleotide sequences represented by SEQ ID NOs. 1 to 200, but also numerous mutants and fragments of nucleotide sequences represented by SEQ ID NOs. 413 to 740, which are called isomiRs, that correspond to these sequences. These mutants can also be obtained as mutants of miRNAs with nucleotide sequences represented by SEQ ID NOs. 1 to 200.

[0285] That is, among the variants of polynucleotides consisting of the base sequence represented by SEQ ID NOs: 1-17, 19-22, 24-27, 39-42, 44-48, 50-52, 54-64, 66, 68, 69, 71, 72, 74-77, 79-92, 94-97, 99, 102, 104-106, 109-125, 127, 128, 130, 132-143, 145, 150-153, 155, 156, 158-170, 173-176, 178, 180, 182-184, 187, 188, 190-200 of the present invention, or the base sequence in which u is t, for example, miRBase(Version 21) The longest variants registered are SEQ ID NOs: 413, 415, 417, 419, 421, 423, 425, 427, 429, 431, 433, 435, 437, 439, 441, 443, 445, 447, 449, 451, 453, 455, 457, 459, 461, 463, 465, 467, 469, 471, 473, 475, 477, 479, 481, 483, 485, 4 87, 489, 491, 493, 495, 497, 499, 501, 503, 505, 507, 509, 511, 513, 515, 517, 519, 521, 523, 525, 527, 529, 531, 533, 535, 537, 539, 541, 543, 545, 547, 549, 551, 553, 555, 557, 559, 561, 563, 565, 567, 569, 571, 573, 5 75, 577, 579, 581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617, 619, 621, 623, 625, 627, 629, 631, 633, 635, 637, 639, 641, 643, 645, 647, 649, 651, 653, 655, 657, 659, 661, Examples of polynucleotides represented by 663, 665, 667, 669, 671, 673, 675, 677, 679, 681, 683, 685, 687, 689, 691, 693, 695, 697, 699, 701, 703, 705, 707, 709, 711, 713, 715, 717, 719, 721, 723, 725, 727, 729, 731, 733, 735, 737, and 739 include polynucleotides represented by 663, 665, 667, 669, 671, 673, 675, 677, 679, 681, 683, 685, 687, 689, 691, 693, 685, 687, 689, 691, 673, 675, 677, 679, 681, 683, 685, 687, 689, 691, 693, 725, 727, 729, 731, 733, 735, 737, and 739.Similarly, the shortest variants are, respectively, sequence numbers 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456, 458, 460, 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, and 48. 8, 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, 558, 560, 562, 564, 566, 568, 570, 572, 574, 57 6, 578, 580, 582, 584, 586, 588, 590, 592, 594, 596, 598, 600, 602, 604, 606, 608, 610, 612, 614, 616, 618, 620, 622, 624, 626, 628, 630, 632, 634, 636, 638, 640, 642, 644, 646, 648, 650, 652, 654, 656, 658, 660, 662, 66 Examples of polynucleotides include sequences represented by 4, 666, 668, 670, 672, 674, 676, 678, 680, 682, 684, 686, 688, 690, 692, 694, 696, 698, 700, 702, 704, 706, 708, 710, 712, 714, 716, 718, 720, 722, 724, 726, 728, 730, 732, 734, 736, 738, and 740. In addition to these variants and fragments, miRBase has registered numerous polynucleotides that are isomiRs corresponding to miRNAs of base sequences represented by any of the sequence numbers 1 to 200. Furthermore, examples of polynucleotides containing base sequences represented by any of the sequence numbers 1 to 200 include the precursor polynucleotides represented by any of the sequence numbers 201 to 412.

[0286] Table 1 lists the names of genes / miRNAs consisting of nucleotide sequences represented by sequence numbers 1 to 740, along with their miRBase Accession No. (registration number).

[0287] As used herein, "specifically bindable" means that the nucleic acid probe or primer used in the present invention binds to a specific target nucleic acid and cannot substantially bind to other nucleic acids.

[0288] [Table 1] TIFF0007862797000002.tif229103TIFF0007862797000003.tif226103TIFF0007862797000004.tif227103TIFF0007862797000005.tif228103TIFF0007862797000006.tif227103TIFF0007862797000007.tif227103TIFF0007862797000008.tif253115TIFF0007862797000009.tif228103TIFF0007862797000010.tif229103TIFF0007862797000011.tif229102TIFF0007862797000012.tif227103TIFF0007862797000013.tif228103TIFF0007862797000014.tif226103TIFF0007862797000015.tif229103TIFF0007862797000016.tif229103TIFF0007862797000017.tif226103TIFF0007862797000018.tif226102TIFF0007862797000019.tif228103TIFF0007862797000020.tif226103TIFF0007862797000021.tif22102

[0289] This specification incorporates the disclosure of Japanese Patent Application No. 2020-064383, which is the basis of the priority of the present application. [Advantages of the Invention]

[0290] This invention makes it possible to detect hippocampal atrophy with high accuracy (or AUC), sensitivity, and specificity, and to distinguish between individuals with hippocampal atrophy and individuals with a normal hippocampus (individuals without hippocampal atrophy). [Brief explanation of the drawing]

[0291] [Figure 1] Figure 1 shows the relationship between the nucleotide sequences of the precursor hsa-mir-1915, represented by sequence number 379, and the resulting products hsa-miR-1915-5p, represented by sequence number 166, and hsa-miR-1915-3p, represented by sequence number 196. [Figure 2] Figures 2A and 2B are discriminant score diagrams for the training sample group (A) and cross-validation sample group (B) obtained in Example 6. Figures 2C and 2D are ROC curves for the training sample group (C) and cross-validation sample group (D). [Figure 3] Figure 3 shows the regression line obtained in Example 7-(2) using hippocampal quantitative values ​​and explanatory variables. Figure 3A is the training and cross-validation sample group, and Figure 3B is the independent validation sample group. [Modes for carrying out the invention]

[0292] The present invention will be described in more detail below. 1. Target nucleic acids for hippocampal atrophy The target nucleic acids used as hippocampal atrophy markers for detecting hippocampal atrophy, or hippocampal atrophy or non-atrophy, using the nucleic acids for hippocampal atrophy detection as defined above in the present invention, for example, nucleic acid probes or primers, are miR-3131, miR-6757-5p, miR-4706, miR-5001-5p, miR-3180-3p, miR-642b-3p, miR-4655-5p, miR-6819-5p, miR-937-5p, miR-4688, miR-6741-5p, miR-7107-5p, miR-4271, miR-1229-5p, miR- 4707-5p, miR-6808-5p, miR-4656, miR-6076, miR-6762-5p, miR-7109-5p, miR-6732-5p, miR-3195, miR-7150, miR-642a-3p, miR-1249-5p, miR-3185 , miR-4689, miR-3141, miR-6840-3p, miR-3135b, miR-1914-3p, miR-4446-3p, miR-4433b-3p, miR-6877-5p, miR-6848-5p, miR-3620-5p, miR-6825-5 p, miR-5739, miR-3663-3p, miR-4695-5p, miR-3162-5p, miR-3679-5p, miR-8059, miR-7110-5p, miR-1275, miR-6779-5p, miR-197-5p, miR-6845-5p , miR-4327, miR-4723-5p, miR-4530, miR-6771-5p, miR-614, miR-92a-2-5p, miR-6891-5p, miR-6124, miR-4687-3p, miR-4442, miR-7977, miR-6785- 5p, miR-4497, miR-8071, miR-663b, miR-3180, miR-4251, miR-1285-3p, miR-6870-5p, miR-4484, miR-4476, miR-6749-5p, miR-4454, miR-6893-5p, m iR-6085, miR-4787-5p, miR-149-3p, miR-7704, miR-6125, miR-6090, miR-3197, miR-6850-5p, miR-4467, miR-6885-5p, miR-6803-5p, miR-6798-5p,miR-6780b-5p, miR-6768-5p, miR-5100, miR-6724-5p, miR-6879-5p, miR-7108-5p, miR-46 49-5p, miR-4739, miR-6089, miR-1908-5p, miR-4516, miR-2861, miR-4492, miR-4294, miR- It may be a polynucleotide that is at least one miRNA selected from the group consisting of 6791-5p, miR-1469, miR-6752-5p, miR-4730, miR-6126, miR-6869-5p, miR-1268a, miR-6799-5p, miR-8069, miR-3621, and miR-4763-3p.

[0293] Examples of major target nucleic acids as such hippocampal atrophy markers include hsa-miR-3131, hsa-miR-6757-5p, hsa-miR-4706, hsa-miR-5001-5p, hsa-miR-3180-3p, hsa-miR-642b-3p, hsa-miR-4655-5p, hsa-miR-6819-5p, hsa-miR-937-5p, hsa-miR-4688, hsa-miR-6741-5p, hsa-miR-7107-5p, hsa-miR-4271, hsa-miR-1229-5p, hsa-miR-4707-5p, hsa-miR-6808-5p, hsa-miR-4656, hsa-miR-6076, hsa-miR-6762-5p, hsa-miR-7109-5p, hsa-miR-6732-5p, hsa-miR-3195, hsa-miR-7150, hsa-miR-642a-3p, hsa-miR-1249-5p, hsa-miR-3185, hsa-miR-4689, hsa-miR-3141, hsa-miR-6840-3p, hsa-miR-3135b, hsa-miR-1914-3p, hsa-miR-4446-3p, hsa-miR-4433b-3p, hsa-miR-6877-5p, hsa-miR-6848-5p, hsa-miR-3620-5p, hsa-miR-6825-5p, hsa-miR-5739, hsa-miR-3663-3p, hsa-miR-4695-5p, hsa-miR-3162-5p, hsa-miR-3679-5p, hsa-miR-8059, hsa-miR-7110-5p, hsa-miR-1275, hsa-miR-6779-5p, hsa-miR-197-5p, hsa-miR-6845-5p, hsa-miR-4327, hsa-miR-4723-5p, hsa-miR-4530, hsa-miR-6771-5p, hsa-miR-614, hsa-miR-92a-2-5p, hsa-miR-6891-5p, hsa-miR-6124, hsa-miR-4687-3p, hsa-miR-4442, hsa-miR-7977, hsa-miR-6785-5p, hsa-miR-4497, hsa-miR-...hsa-miR-1285-3p, hsa-miR-6870-5p, hsa-miR-4484, hsa-miR-4476, hsa-miR-6749-5p, hsa-miR-445 4, hsa-miR-6893-5p, hsa-miR-6085, hsa-miR-4787-5p, hsa-miR-149-3p, hsa-miR-7704, hsa-miR-61 25, hsa-miR-6090, hsa-miR-3197, hsa-miR-6850-5p, hsa-miR-4467, hsa-miR-6885-5p, hsa-miR-680 3-5p, hsa-miR-6798-5p, hsa-miR-6780b-5p, hsa-miR-6768-5p, hsa-miR-5100, hsa-miR-6724-5p, hs a-miR-6879-5p, hsa-miR-7108-5p, hsa-miR-4649-5p, hsa-miR-4739, hsa-miR-6089, hsa-miR-1908- 5p, hsa-miR-4516, hsa-miR-2861, hsa-miR-4492, hsa-miR-4294, hsa-miR-6791-5p, hsa-miR-1469, h It contains a polynucleotide that is at least one miRNA selected from the group consisting of sa-miR-6752-5p, hsa-miR-4730, hsa-miR-6126, hsa-miR-6869-5p, hsa-miR-1268a, hsa-miR-6799-5p, hsa-miR-8069, hsa-miR-3621, and hsa-miR-4763-3p.

[0294] Furthermore, in combination with these miRNAs, another hippocampal atrophy marker, specifically miR-1228-5p, miR-760, miR-187-5p, miR-7111-5p, miR-6088, miR-6805-3p, miR-4640-5p, miR-6721-5p, miR-6880-5p, miR-711, miR-128-1-5p, miR-4525, miR-486-3p, miR-6756-5p, miR-1260b, miR-3184-5p, miR-6075, miR-204-3p, miR-4728-5p, miR-4534, miR-4758-5p, miR-8063, miR-6836-3p, miR-6789-5p, miR-744-5p, miR-1909-3p, miR-887-3p, miR-4745-5p, miR-4433a-3p, miR-5090, miR-296-5p, miR-939-5p, miR-3648, miR-3196, miR-6722-3p, miR-6805-5p, miR-1202, miR-6775-5p, miR-6087, miR-6765-5p, miR-6875-5p, miR-4674, miR-1233-5p, miR-7114-5p, miR-5787, miR-8072, miR-3619-3p, miR-4632-5p, miR-6800-5p, miR-4634, miR-4486, miR-6727-5p, miR-4505, miR-4725-3p, miR-1538, miR-320b, miR-1915-5p, miR-328-5p, miR-6820-5p, miR-6726-5p, miR-3665, miR-638, miR-762, miR-4466, miR-3940-5p, miR-1237-5p, miR-575, miR-3656, miR-4488, miR-4281, miR-6781-5p, miR-4532, miR-4665-5p, miR-6816-5p, miR-4508, miR-6784-5p, miR-6786-5p, miR-4741, miR-1343-5p, miR-1227-5p, miR-4734, miR-3960, miR-128-2-5p, miR-6743-5p, miR-663a, miR-6729-5p, miR-1915-3p, miR-1268b, miR-4651A polynucleotide, which is at least one miRNA selected from the group consisting of miR-3178 and miR-4463, can also be preferably used as a target nucleic acid.

[0295] Examples of such other hippocampal atrophy markers include hsa-miR-1228-5p, hsa-miR-760, hsa-miR-187-5p, hsa-miR-7111-5p, hsa-miR-6088, hsa-miR-6805-3p, hsa-miR-4640-5p, hsa-miR-6721-5p, hsa-miR-6880-5p, hsa-miR-711, hsa-miR-128-1-5p, hsa-miR-4525, hsa-miR-486-3p, hsa-miR-6756-5p, hsa-miR-1260b, hsa-miR-3184-5p, hsa-miR-6075, hsa-miR-204-3p, hsa-miR-4728-5p, hsa-miR-4534, hsa-miR-4758-5p, hsa-miR-8063, hsa-miR-6836-3p, hsa-miR-6789-5p, hsa-miR-744-5p, hsa-miR-1909-3p, hsa-miR-887-3p, hsa-miR-4745-5p, hsa-miR-4433a-3p, hsa-miR-5090, hsa-miR-296-5p, hsa-miR-939-5p, hsa-miR-3648, hsa-miR-3196, hsa-miR-6722-3p, hsa-miR-6805-5p, hsa-miR-1202, hsa-miR-6775-5p, hsa-miR-6087, hsa-miR-6765-5p, hsa-miR-6875-5p, hsa-miR-4674, hsa-miR-1233-5p, hsa-miR-7114-5p, hsa-miR-5787, hsa-miR-8072, hsa-miR-3619-3p, hsa-miR-4632-5p, hsa-miR-6800-5p, hsa-miR-4634, hsa-miR-4486, hsa-miR-6727-5p, hsa-miR-4505, hsa-miR-4725-3p, hsa-miR-1538, hsa-miR-320b, hsa-miR-1915-5p, hsa-miR-328-5p, hsa-miR-6820-5p, hsa-miR-6726-5p, hsa-miR-3665, hsa-miR-638, hsa-miR-762, hsa-miR-4466, hsa-miR-3940-5p, hsa-miR-1237-5p,hsa-miR-575, hsa-miR-3656, hsa-miR-4488, hsa-miR-4281, hsa-miR-6781-5p, hsa-miR-4532, hsa-miR-4665-5p, hsa- miR-6816-5p, hsa-miR-4508, hsa-miR-6784-5p, hsa-miR-6786-5p, hsa-miR-4741, hsa-miR-1343-5p, hsa-miR-1227-5 It contains a polynucleotide that is at least one miRNA selected from the group consisting of p, hsa-miR-4734, hsa-miR-3960, hsa-miR-128-2-5p, hsa-miR-6743-5p, hsa-miR-663a, hsa-miR-6729-5p, hsa-miR-1915-3p, hsa-miR-1268b, hsa-miR-4651, hsa-miR-3178, and hsa-miR-4463.

[0296] The above miRNAs include human miRNA polynucleotides / genes, namely hsa-miR-3131, hsa-miR-6757-5p, hsa-miR-4706, hsa-miR-5001-5p, hsa-miR-3180-3p, hsa-miR-642b-3p, hsa-miR-4655-5p, hsa-miR-6819-5p, hsa-miR-937-5p, hsa-miR-4688, hsa-miR-6741-5p, hsa-miR-7107-5p, hsa-miR-4271, hsa-miR-1229-5p, hsa-miR-4707-5p, hsa-miR-6808-5p, hsa-miR-4656, hsa-miR-6076, hsa-miR-6762-5p, hsa-miR-7109-5p, hsa-miR-6732-5p, hsa-miR-3195, hsa-miR-7150, hsa-miR-642a-3p, hsa-miR-1249-5p, hsa-miR-3185, hsa-miR-4689, hsa-miR-3141, hsa-miR-6840-3p, hsa-miR-3135b, hsa-miR-1914-3p, hsa-miR-4446-3p, hsa-miR-4433b-3p, hsa-miR-6877-5p, hsa-miR-6848-5p, hsa-miR-3620-5p, hsa-miR-6825-5p, hsa-miR-5739, hsa-miR-3663-3p, hsa-miR-4695-5p, hsa-miR-3162-5p, hsa-miR-3679-5p, hsa-miR-8059, hsa-miR-7110-5p, hsa-miR-1275, hsa-miR-6779-5p, hsa-miR-197-5p, hsa-miR-6845-5p, hsa-miR-4327, hsa-miR-4723-5p, hsa-miR-4530, hsa-miR-6771-5p, hsa-miR-614, hsa-miR-92a-2-5p, hsa-miR-6891-5p, hsa-miR-6124, hsa-miR-4687-3p, hsa-miR-4442, hsa-miR-7977, hsa-miR-6785-5p, hsa-miR-4497, hsa-miR-8071, hsa-miR-663b, hsa-miR-3180, hsa-miR-4251,hsa-miR-1285-3p, hsa-miR-6870-5p, hsa-miR-4484, hsa-miR-4476, hsa-miR-6749-5p, hsa-miR-4454, hsa-miR-6893-5p, hsa-miR-6085, hsa-miR- 4787-5p, hsa-miR-149-3p, hsa-miR-7704, hsa-miR-6125, hsa-miR-6090, hsa-miR-3197, hsa-miR-6850-5p, hsa-miR-4467, hsa-miR-6885-5p, hsa- miR-6803-5p, hsa-miR-6798-5p, hsa-miR-6780b-5p, hsa-miR-6768-5p, hsa-miR-5100, hsa-miR-6724-5p, hsa-miR-6879-5p, hsa-miR-7108-5p, hs a-miR-4649-5p, hsa-miR-4739, hsa-miR-6089, hsa-miR-1908-5p, hsa-miR-4516, hsa-miR-2861, hsa-miR-4492, hsa-miR-4294, hsa-miR-6791-5p, h sa-miR-1469, hsa-miR-6752-5p, hsa-miR-4730, hsa-miR-6126, hsa-miR-6869-5p, hsa-miR-1268a, hsa-miR-6799-5p, hsa-miR-8069, hsa-miR-362 1hsa-miR-4763-3p, hsa-miR-1228-5p, hsa-miR-760, hsa-miR-187-5p, hsa-miR-7111-5p, hsa-miR-6088, hsa-miR-6805-3p, hsa-miR-4640-5p, hsa- miR-6721-5p, hsa-miR-6880-5p, hsa-miR-711, hsa-miR-128-1-5p, hsa-miR-4525, hsa-miR-486-3p, hsa-miR-6756-5p, hsa-miR-1260b, hsa-miR-3 184-5p, hsa-miR-6075, hsa-miR-204-3p, hsa-miR-4728-5p, hsa-miR-4534, hsa-miR-4758-5p, hsa-miR-8063, hsa-miR-6836-3p, hsa-miR-6789-5phsa-miR-744-5p, hsa-miR-1909-3p, hsa-miR-887-3p, hsa-miR-4745-5p, hsa-miR-4433a-3p, hsa-miR-5090, hsa-miR-296-5p, hsa-miR-939-5p, hsa-miR-3648, hsa-miR-3196, hsa-miR-6722-3p, hsa-miR-6805-5p, hsa-miR-1202, hsa-miR-6775-5p, hsa-miR-6087, hsa-miR-6765-5p hsa-miR-6875-5p hsa-miR-4674 hsa-miR-1233-5p hsa-miR-7114-5p hsa-miR-5787 hsa-miR-8072 hsa-miR-3619-3p hsa-miR-4632-5p hsa-miR-6800-5p hsa-miR-4634 hsa-miR-4486 hsa-miR-6727-5p hsa-miR-4505 hsa-miR-4725-3p hsa-miR-1538 hsa-miR-320b hsa- miR-1915-5p, hsa-miR-328-5p, hsa-miR-6820-5p, hsa-miR-6726-5p, hsa-miR-3665, hsa-miR-638, hsa-miR-762, hsa-miR-4466, hsa-miR-3940-5p, hsa-miR-1237-5p, hsa-miR-575, hsa-miR-3656, hsa-miR-4488, hsa-miR-4281, hsa-miR-6781-5p, hsa-miR-4532, hsa-miR-4665-5p hsa-miR-6816-5p, hsa-miR-4508, hsa-miR-6784-5p, hsa-miR-6786-5p, hsa-miR-4741, hsa-miR-1343-5p, hsa-miR-1227-5p, hsa-miR-4734, hsa-miR-3960, hsa-miR-128-2-5p, hsa-miR-6743-5p, hsa-miR-663a, hsa-miR-6729-5p, hsa-miR-1915-3p, hsa-miR-1268b, hsa-miR-4651This includes polynucleotides / genes containing the base sequences represented by any of SEQ ID NOs: 1-200, corresponding to hsa-miR-3178 and hsa-miR-4463, respectively, as well as their homologs, transcripts, and variants or derivatives. Here, genes, homologs, transcripts, variants, and derivatives are defined as described above.

[0297] Preferred target nucleic acids are human miRNA polynucleotides / genes containing a base sequence represented by any of SEQ ID NOs: 1 to 200, their transcripts, and more preferably the transcripts, i.e., miRNA, and its precursor RNA, pri-miRNA or pre-miRNA.

[0298] The primary target genes are the hsa-miR-3131 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0299] The second target gene is the hsa-miR-6757-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0300] The third target gene is the hsa-miR-4706 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0301] The fourth target gene is the hsa-miR-5001-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0302] The fifth target gene is the hsa-miR-3180-3p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0303] The sixth target gene is the hsa-miR-642b-3p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0304] The seventh target gene is the hsa-miR-4655-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0305] The eighth target gene is the hsa-miR-6819-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0306] The ninth target gene is the hsa-miR-937-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0307] The tenth target gene is the hsa-miR-4688 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0308] The eleventh target gene is the hsa-miR-6741-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0309] The twelfth target gene is the hsa-miR-7107-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0310] The 13th target gene is the hsa-miR-4271 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0311] The 14th target gene is the hsa-miR-1229-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0312] The 15th target gene is the hsa-miR-4707-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0313] The 16th target gene is the hsa-miR-6808-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0314] The 17th target gene is the hsa-miR-4656 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0315] The 18th target gene is the hsa-miR-6076 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0316] The 19th target gene is the hsa-miR-6762-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0317] The 20th target gene is the hsa-miR-7109-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0318] The 21st target gene is the hsa-miR-6732-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0319] The 22nd target gene is the hsa-miR-3195 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0320] The 23rd target gene is the hsa-miR-7150 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0321] The 24th target gene is the hsa-miR-642a-3p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0322] The 25th target gene is the hsa-miR-1249-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0323] The 26th target gene is the hsa-miR-3185 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0324] The 27th target gene is the hsa-miR-4689 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0325] The 28th target gene is the hsa-miR-3141 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0326] The 29th target gene is the hsa-miR-6840-3p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0327] The 30th target gene is the hsa-miR-3135b gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0328] The 31st target gene is the hsa-miR-1914-3p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0329] The 32nd target gene is the hsa-miR-4446-3p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0330] The 33rd target gene is the hsa-miR-4433b-3p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0331] The 34th target gene is the hsa-miR-6877-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0332] The 35th target gene is the hsa-miR-6848-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0333] The 36th target gene is the hsa-miR-3620-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0334] The 37th target gene is the hsa-miR-6825-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0335] The 38th target gene is the hsa-miR-5739 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0336] The 39th target gene is the hsa-miR-3663-3p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0337] The 40th target gene is the hsa-miR-4695-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0338] The 41st target gene is the hsa-miR-3162-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0339] The 42nd target gene is the hsa-miR-3679-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0340] The 43rd target gene is the hsa-miR-8059 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0341] The 44th target gene is the hsa-miR-7110-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0342] The 45th target gene is the hsa-miR-1275 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0343] The 46th target gene is the hsa-miR-6779-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0344] The 47th target gene is the hsa-miR-197-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0345] The 48th target gene is the hsa-miR-6845-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0346] The 49th target gene is the hsa-miR-4327 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0347] The 50th target gene is the hsa-miR-4723-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0348] The 51st target gene is the hsa-miR-4530 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0349] The 52nd target gene is the hsa-miR-6771-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0350] The 53rd target gene is the hsa-miR-614 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0351] The 54th target gene is the hsa-miR-92a-2-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0352] The 55th target gene is the hsa-miR-6891-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0353] The 56th target gene is the hsa-miR-6124 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0354] The 57th target gene is the hsa-miR-4687-3p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0355] The 58th target gene is the hsa-miR-4442 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0356] The 59th target gene is the hsa-miR-7977 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0357] The 60th target gene is the hsa-miR-6785-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0358] The 61st target gene is the hsa-miR-4497 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0359] The 62nd target gene is the hsa-miR-8071 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0360] The 63rd target gene is the hsa-miR-663b gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0361] The 64th target gene is the hsa-miR-3180 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0362] The 65th target gene is the hsa-miR-4251 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0363] The 66th target gene is the hsa-miR-1285-3p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0364] The 67th target gene is the hsa-miR-6870-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0365] The 68th target gene is the hsa-miR-4484 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0366] The 69th target gene is the hsa-miR-4476 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0367] The 70th target gene is the hsa-miR-6749-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0368] The 71st target gene is the hsa-miR-4454 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0369] The 72nd target gene is the hsa-miR-6893-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0370] The 73rd target gene is the hsa-miR-6085 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0371] The 74th target gene is the hsa-miR-4787-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0372] The 75th target gene is the hsa-miR-149-3p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0373] The 76th target gene is the hsa-miR-7704 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0374] The 77th target gene is the hsa-miR-6125 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0375] The 78th target gene is the hsa-miR-6090 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0376] The 79th target gene is the hsa-miR-3197 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0377] The 80th target gene is the hsa-miR-6850-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0378] The 81st target gene is the hsa-miR-4467 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0379] The 82nd target gene is the hsa-miR-6885-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0380] The 83rd target gene is the hsa-miR-6803-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0381] The 84th target gene is the hsa-miR-6798-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0382] The 85th target gene is the hsa-miR-6780b-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0383] The 86th target gene is the hsa-miR-6768-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0384] The 87th target gene is the hsa-miR-5100 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0385] The 88th target gene is the hsa-miR-6724-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0386] The 89th target gene is the hsa-miR-6879-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0387] The 90th target gene is the hsa-miR-7108-5p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0388] The 91st target gene is the hsa-miR-4649-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0389] The 92nd target gene is the hsa-miR-4739 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0390] The 93rd target gene is the hsa-miR-6089 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0391] The 94th target gene is the hsa-miR-1908-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0392] The 95th target gene is the hsa-miR-4516 gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0393] The 96th target gene is the hsa-miR-2861 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0394] The 97th target gene is the hsa-miR-4492 gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0395] The 98th target gene is the hsa-miR-4294 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0396] The 99th target gene is the hsa-miR-6791-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0397] The 100th target gene is the hsa-miR-1469 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0398] The 101st target gene is the hsa-miR-6752-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0399] The 102nd target gene is the hsa-miR-4730 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0400] The 103rd target gene is the hsa-miR-6126 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0401] The 104th target gene is the hsa-miR-6869-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0402] The 105th target gene is the hsa-miR-1268a gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0403] The 106th target gene is the hsa-miR-6799-5p gene, its congeners, their transcripts, or their mutants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0404] The 107th target gene is the hsa-miR-8069 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0405] The 108th target gene is the hsa-miR-3621 gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0406] The 109th target gene is the hsa-miR-4763-3p gene, its congeners, their transcripts, or their variants or derivatives. To date, there are no known reports that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy.

[0407] The 110th target gene is the hsa-miR-1228-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0408] The 111th target gene is the hsa-miR-760 gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 5).

[0409] The 112th target gene is the hsa-miR-187-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 7).

[0410] The 113th target gene is the hsa-miR-7111-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0411] The 114th target gene is the hsa-miR-6088 gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0412] The 115th target gene is the hsa-miR-6805-3p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0413] The 116th target gene is the hsa-miR-4640-5p gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0414] The 117th target gene is the hsa-miR-6721-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0415] The 118th target gene is the hsa-miR-6880-5p gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0416] The 119th target gene is the hsa-miR-711 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 7).

[0417] The 120th target gene is the hsa-miR-128-1-5p gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 7).

[0418] The 121st target gene is the hsa-miR-4525 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0419] The 122nd target gene is the hsa-miR-486-3p gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 2).

[0420] The 123rd target gene is the hsa-miR-6756-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0421] The 124th target gene is the hsa-miR-1260b gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0422] The 125th target gene is the hsa-miR-3184-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0423] The 126th target gene is the hsa-miR-6075 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0424] The 127th target gene is the hsa-miR-204-3p gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Non-Patent Literature 5).

[0425] The 128th target gene is the hsa-miR-4728-5p gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0426] The 129th target gene is the hsa-miR-4534 gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0427] The 130th target gene is the hsa-miR-4758-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0428] The 131st target gene is the hsa-miR-8063 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0429] The 132nd target gene is the hsa-miR-6836-3p gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0430] The 133rd target gene is the hsa-miR-6789-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0431] The 134th target gene is the hsa-miR-744-5p gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0432] The 135th target gene is the hsa-miR-1909-3p gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0433] The 136th target gene is the hsa-miR-887-3p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 5).

[0434] The 137th target gene is the hsa-miR-4745-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0435] The 138th target gene is the hsa-miR-4433a-3p gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0436] The 139th target gene is the hsa-miR-5090 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0437] The 140th target gene is the hsa-miR-296-5p gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript can serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0438] The 141st target gene is the hsa-miR-939-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0439] The 142nd target gene is the hsa-miR-3648 gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript can serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0440] The 143rd target gene is the hsa-miR-3196 gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0441] The 144th target gene is the hsa-miR-6722-3p gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript may serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Non-Patent Literature 4).

[0442] The 145th target gene is the hsa-miR-6805-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 3).

[0443] The 146th target gene is the hsa-miR-1202 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0444] The 147th target gene is the hsa-miR-6775-5p gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0445] The 148th target gene is the hsa-miR-6087 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0446] The 149th target gene is the hsa-miR-6765-5p gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0447] The 150th target gene is the hsa-miR-6875-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0448] The 151st target gene is the hsa-miR-4674 gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Non-Patent Literature 4).

[0449] The 152nd target gene is the hsa-miR-1233-5p gene, its homologs, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript can serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0450] The 153rd target gene is the hsa-miR-7114-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0451] The 154th target gene is the hsa-miR-5787 gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0452] The 155th target gene is the hsa-miR-8072 gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0453] The 156th target gene is the hsa-miR-3619-3p gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0454] The 157th target gene is the hsa-miR-4632-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0455] The 158th target gene is the hsa-miR-6800-5p gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0456] The 159th target gene is the hsa-miR-4634 gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0457] The 160th target gene is the hsa-miR-4486 gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript can serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0458] The 161st target gene is the hsa-miR-6727-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0459] The 162nd target gene is the hsa-miR-4505 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0460] The 163rd target gene is the hsa-miR-4725-3p gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0461] The 164th target gene is the hsa-miR-1538 gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0462] The 165th target gene is the hsa-miR-320b gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 4).

[0463] The 166th target gene is the hsa-miR-1915-5p gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0464] The 167th target gene is the hsa-miR-328-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 7).

[0465] The 168th target gene is the hsa-miR-6820-5p gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0466] The 169th target gene is the hsa-miR-6726-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0467] The 170th target gene is the hsa-miR-3665 gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0468] The 171st target gene is the hsa-miR-638 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0469] The 172nd target gene is the hsa-miR-762 gene, its homologs, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript can serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0470] The 173rd target gene is the hsa-miR-4466 gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0471] The 174th target gene is the hsa-miR-3940-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0472] The 175th target gene is the hsa-miR-1237-5p gene, its homologs, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0473] The 176th target gene is the hsa-miR-575 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0474] The 177th target gene is the hsa-miR-3656 gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript can serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0475] The 178th target gene is the hsa-miR-4488 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0476] The 179th target gene is the hsa-miR-4281 gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0477] The 180th target gene is the hsa-miR-6781-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0478] The 181st target gene is the hsa-miR-4532 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0479] The 182nd target gene is the hsa-miR-4665-5p gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0480] The 183rd target gene is the hsa-miR-6816-5p gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0481] The 184th target gene is the hsa-miR-4508 gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0482] The 185th target gene is the hsa-miR-6784-5p gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0483] The 186th target gene is the hsa-miR-6786-5p gene, its homologs, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript can serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0484] The 187th target gene is the hsa-miR-4741 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0485] The 188th target gene is the hsa-miR-1343-5p gene, its homologs, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0486] The 189th target gene is the hsa-miR-1227-5p gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript can serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0487] The 190th target gene is the hsa-miR-4734 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0488] The 191st target gene is the hsa-miR-3960 gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0489] The 192nd target gene is the hsa-miR-128-2-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 7).

[0490] The 193rd target gene is the hsa-miR-6743-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0491] The 194th target gene is the hsa-miR-663a gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Non-Patent Literature 3).

[0492] The 195th target gene is the hsa-miR-6729-5p gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0493] The 196th target gene is the hsa-miR-1915-3p gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript may serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0494] The 197th target gene is the hsa-miR-1268b gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0495] The 198th target gene is the hsa-miR-4651 gene, its homologs, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0496] The 199th target gene is the hsa-miR-3178 gene, its congeners, their transcripts, or their variants or derivatives. Previous reports have indicated that changes in the expression of this gene or its transcript can serve as markers for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 1).

[0497] The 200th target gene is the hsa-miR-4463 gene, its congeners, their transcripts, or their variants or derivatives. It has been reported that changes in the expression of this gene or its transcript can serve as a marker for hippocampal atrophy or diseases characterized by hippocampal atrophy (Patent Document 6).

[0498] 2. Nucleic acids for detecting hippocampal atrophy In the present invention, the nucleic acids for detecting hippocampal atrophy, for example, nucleic acids usable to diagnose hippocampal atrophy, such as nucleic acid probes or primers, are target nucleic acids for hippocampal atrophy (hippocampal atrophy markers), such as miR-3131, miR-6757-5p, miR-4706, miR-5001-5p, miR-3180-3p, miR-642b-3p, miR-4655-5p, miR-6819-5p, miR-937-5p, miR-4688, miR-6741-5p, miR-7107-5p, miR-4271, miR-1229-5p, and miR-4707-5. p, miR-6808-5p, miR-4656, miR-6076, miR-6762-5p, miR-7109-5p, miR-6732-5p, miR-3195, miR-7150, miR-642a-3p, miR-1249-5p, miR-3185, miR-46 89, miR-3141, miR-6840-3p, miR-3135b, miR-1914-3p, miR-4446-3p, miR-4433b-3p, miR-6877-5p, miR-6848-5p, miR-3620-5p, miR-6825-5p, miR-57 39, miR-3663-3p, miR-4695-5p, miR-3162-5p, miR-3679-5p, miR-8059, miR-7110-5p, miR-1275, miR-6779-5p, miR-197-5p, miR-6845-5p, miR-4327, miR-4723-5p, miR-4530, miR-6771-5p, miR-614, miR-92a-2-5p, miR-6891-5p, miR-6124, miR-4687-3p, miR-4442, miR-7977, miR-6785-5p, miR-4497 , miR-8071, miR-663b, miR-3180, miR-4251, miR-1285-3p, miR-6870-5p, miR-4484, miR-4476, miR-6749-5p, miR-4454, miR-6893-5p, miR-6085, miR- 4787-5p, miR-149-3p, miR-7704, miR-6125, miR-6090, miR-3197, miR-6850-5p, miR-4467, miR-6885-5p, miR-6803-5p, miR-6798-5p, miR-6780b-5p,miR-6768-5p, miR-5100, miR-6724-5p, miR-6879-5p, miR-7108-5p, miR-4649-5p, miR-4739, m iR-6089, miR-1908-5p, miR-4516, miR-2861, miR-4492, miR-4294, miR-6791-5p, miR-1469, miR It may be a polynucleotide that is at least one miRNA selected from the group consisting of -6752-5p, miR-4730, miR-6126, miR-6869-5p, miR-1268a, miR-6799-5p, miR-8069, miR-3621, and miR-4763-3p, or a nucleic acid that specifically binds to the complementary strand of said polynucleotide.

[0499] In one embodiment, nucleic acids, such as nucleic acid probes or primers, that can be used to detect or diagnose hippocampal atrophy are human-derived hsa-miR-3131, hsa-miR-6757-5p, hsa-miR-4706, hsa-miR-5001-5p, hsa-miR-3180-3p, hsa-miR-642b-3p, hsa-miR-4655-5p, hsa-miR-6819-5p, hsa-miR-937-5p, hsa-miR-4688, hsa-miR-6741-5p, hsa-miR-7107- 5p, hsa-miR-4271, hsa-miR-1229-5p, hsa-miR-4707-5p, hsa-miR-6808-5p, hsa-miR-4656, hsa-miR-6076, hsa-miR-6762-5p, hsa-miR-7109-5p, hs a-miR-6732-5p, hsa-miR-3195, hsa-miR-7150, hsa-miR-642a-3p, hsa-miR-1249-5p, hsa-miR-3185, hsa-miR-4689, hsa-miR-3141, hsa-miR-6840- 3p, hsa-miR-3135b, hsa-miR-1914-3p, hsa-miR-4446-3p, hsa-miR-4433b-3p, hsa-miR-6877-5p, hsa-miR-6848-5p, hsa-miR-3620-5p, hsa-miR-68 25-5p, hsa-miR-5739, hsa-miR-3663-3p, hsa-miR-4695-5p, hsa-miR-3162-5p, hsa-miR-3679-5p, hsa-miR-8059, hsa-miR-7110-5p, hsa-miR-1275 , hsa-miR-6779-5p, hsa-miR-197-5p, hsa-miR-6845-5p, hsa-miR-4327, hsa-miR-4723-5p, hsa-miR-4530, hsa-miR-6771-5p, hsa-miR-614, hsa-mi R-92a-2-5p, hsa-miR-6891-5p, hsa-miR-6124, hsa-miR-4687-3p, hsa-miR-4442, hsa-miR-7977, hsa-miR-6785-5p, hsa-miR-4497, hsa-miR-8071,hsa-miR-663b, hsa-miR-3180, hsa-miR-4251, hsa-miR-1285-3p, hsa-miR-6870-5p, hsa-miR-4484, hsa-miR-4 476, hsa-miR-6749-5p, hsa-miR-4454, hsa-miR-6893-5p, hsa-miR-6085, hsa-miR-4787-5p, hsa-miR-149-3p, hsa-miR-7704, hsa-miR-6125, hsa-miR-6090, hsa-miR-3197, hsa-miR-6850-5p, hsa-miR-4467, hsa-miR-6885 -5p, hsa-miR-6803-5p, hsa-miR-6798-5p, hsa-miR-6780b-5p, hsa-miR-6768-5p, hsa-miR-5100, hsa-miR-6724 -5p, hsa-miR-6879-5p, hsa-miR-7108-5p, hsa-miR-4649-5p, hsa-miR-4739, hsa-miR-6089, hsa-miR-1908-5p , hsa-miR-4516, hsa-miR-2861, hsa-miR-4492, hsa-miR-4294, hsa-miR-6791-5p, hsa-miR-1469, hsa-miR-6752 The nucleic acid may be a nucleic acid that specifically binds to a polynucleotide that is at least one miRNA selected from the group consisting of -5p, hsa-miR-4730, hsa-miR-6126, hsa-miR-6869-5p, hsa-miR-1268a, hsa-miR-6799-5p, hsa-miR-8069, hsa-miR-3621, and hsa-miR-4763-3p, or to the complementary strand of said polynucleotide. If the nucleic acid is a primer, it may be a nucleic acid that specifically binds to the aforementioned polynucleotide that is a miRNA or the complementary strand of said polynucleotide and is capable of amplifying it. The primer may also be a set of primers, such as a primer pair, that specifically binds to the aforementioned polynucleotide that is a miRNA or the complementary strand of said polynucleotide and is capable of amplifying it.

[0500] The above hippocampal atrophy marker miRNA is another hippocampal atrophy marker, miR-1228-5p, miR-760, miR-187-5p, miR-7111-5p, miR-6088, miR-6805-3p, miR-4640-5p, miR-6721-5p, miR-6880-5p, miR-711, miR-128-1-5p, miR-4525, miR-486-3p, miR-6756-5p, miR-1260b, miR-3184-5p, miR-6075, miR-204-3p, miR-4728-5p, miR-4534, miR-4758-5p, miR-8063, miR-6836-3p, miR-6789-5p, miR-744-5p, miR-1909-3p, miR-887-3p, miR-4745-5p, miR-4433a-3p, miR-5090, miR-296-5p, miR-939-5p, miR-3648, miR-3196, miR-6722-3p, miR-6805-5p, miR-1202, miR-6775-5p, miR-6087, miR-6765-5p, miR-6875-5p, miR-4674, miR-1233-5p, miR-7114-5p, miR-5787, miR-8072, miR-3619-3p, miR-4632-5p, miR-6800-5p, miR-4634, miR-4486, miR-6727-5p, miR-4505, miR-4725-3p, miR-1538, miR-320b, miR-1915-5p, miR-328-5p, miR-6820-5p, miR-6726-5p, miR-3665, miR-638, miR-762, miR-4466, miR-3940-5p, miR-1237-5p, miR-575, miR-3656, miR-4488, miR-4281, miR-6781-5p, miR-4532, miR-4665-5p, miR-6816-5p, miR-4508, miR-6784-5p, miR-6786-At least one polynucleotide selected from the group consisting of miR-3178 and miR-4463, or a complementary strand of said polynucleotide, can be used in combination with a nucleic acid that can specifically bind to it to detect hippocampal atrophy.

[0501] For example, hsa-miR-1228-5p, hsa-miR-760, hsa-miR-187-5p, hsa-miR-7111-5p, hsa-miR-6088, hsa-miR-6805-3p, hsa-miR-4640-5p, hsa-miR-6721-5p, hsa-miR-6880-5p, hsa-miR-711, hsa-miR-128-1-5p, hsa-miR-4525, hsa-miR-486-3p, hsa-miR-6756-5p, hsa-miR-1260b, hsa-miR-3184-5p, hsa-miR-6075, hsa-miR-204-3p, hsa-miR-4728-5p, hsa-miR-4534, hsa-miR-4758-5p, hsa-miR-8063, hsa-miR-6836-3p, hsa-miR-6789-5p, hsa-miR-744-5p, hsa-miR-1909-3p, hsa-miR-887-3p, hsa-miR-4745-5p, hsa-miR-4433a-3p, hsa-miR-5090, hsa-miR-296-5p, hsa-miR-939-5p, hsa-miR-3648, hsa-miR-3196, hsa-miR-6722-3p, hsa-miR-6805-5p, hsa-miR-1202, hsa-miR-6775-5p, hsa-miR-6087, hsa-miR-6765-5p, hsa-miR-6875-5p, hsa-miR-4674, hsa-miR-1233-5p, hsa-miR-7114-5p, hsa-miR-5787, hsa-miR-8072, hsa-miR-3619-3p, hsa-miR-4632-5p, hsa-miR-6800-5p, hsa-miR-4634, hsa-miR-4486, hsa-miR-6727-5p, hsa-miR-4505, hsa-miR-4725-3p, hsa-miR-1538, hsa-miR-320b, hsa-miR-1915-5p, hsa-miR-328-5p, hsa-miR-6820-5p, hsa-miR-6726-5p, hsa-miR-3665, hsa-miR-638, hsa-miR-762, hsa-miR-4466, hsa-miR-3940-5p, hsa-miR-1237-5p, hsa-miR-575, hsa-miR-3656hsa-miR-4488, hsa-miR-4281, hsa-miR-6781-5p, hsa-miR-4532, hsa-miR-4665-5p, hsa-miR-6816-5p, hsa-miR-4508, hsa-miR- 6784-5p, hsa-miR-6786-5p, hsa-miR-4741, hsa-miR-1343-5p, hsa-miR-1227-5p, hsa-miR-4734, hsa-miR-3960, hsa-miR-128-2- At least one polynucleotide selected from the group consisting of 5p, hsa-miR-6743-5p, hsa-miR-663a, hsa-miR-6729-5p, hsa-miR-1915-3p, hsa-miR-1268b, hsa-miR-4651, hsa-miR-3178, and hsa-miR-4463, or a nucleic acid that can specifically bind to the complementary strand of said polynucleotide, can be used in combination with the above-mentioned hippocampal atrophy markers to detect hippocampal atrophy.

[0502] The above-mentioned nucleic acids for detecting hippocampal atrophy, such as nucleic acid probes or primers, are capable of detecting hippocampal atrophy markers and, either alone or in combination of two or more, enable the qualitative and / or quantitative measurement of the presence, expression level, or abundance of the above-mentioned miRNAs, such as polynucleotides / genes containing the base sequences represented by SEQ ID NOs: 1-200, as well as their homologs, transcripts, or variants or derivatives.

[0503] In one embodiment, the nucleic acids usable in the present invention, such as nucleic acid probes or primers, are nucleic acid probes that can specifically bind to a polynucleotide consisting of a base sequence represented by at least one of SEQ ID NOs: 1 to 109, or to the complementary strand of said polynucleotide, or primers that can amplify a polynucleotide consisting of a base sequence represented by at least one of SEQ ID NOs: 1 to 109.

[0504] In one embodiment, the nucleic acids usable in the present invention, such as nucleic acid probes or primers, may further include a nucleic acid probe that can specifically bind to a polynucleotide consisting of a base sequence represented by at least one of SEQ ID NOs: 110 to 200, or to the complementary strand of said polynucleotide, or a primer capable of amplifying a polynucleotide consisting of a base sequence represented by at least one of SEQ ID NOs: 110 to 200.

[0505] In one embodiment, the nucleic acids usable in the present invention, such as nucleic acid probes or primers, include a group of polynucleotides comprising a base sequence represented by any of SEQ ID NOs: 1 to 740, or a base sequence in which u is t, and a group of complementary polynucleotides thereof; a group of polynucleotides that hybridize with DNA consisting of a base sequence complementary to the said base sequence under stringent conditions (described later), and a group of polynucleotides thereof, and a group of polynucleotides that contain 15 or more, preferably 17 or more consecutive bases in the base sequences of those polynucleotide groups, and a combination of one or more polynucleotides selected from these groups. These polynucleotides can be used as nucleic acids, such as nucleic acid probes or primers, for detecting miRNA, which is the target nucleic acid and a hippocampal atrophy marker.

[0506] In one embodiment, an example of a nucleic acid usable in the present invention, such as a nucleic acid probe or primer, is one or more polynucleotides selected from the group consisting of the following polynucleotides (a) to (e): (a) A polynucleotide consisting of a base sequence represented by any of Sequence IDs 1 to 109, or a base sequence in which u is t, a variant thereof, a derivative thereof, a fragment thereof containing 15 or more consecutive bases, (b) Polynucleotides comprising a base sequence represented by any of SEQ ID NOs: 1 to 109, variants thereof, derivatives thereof, or fragments thereof comprising 15 or more consecutive bases (c) A polynucleotide consisting of a nucleotide sequence complementary to any of the nucleotide sequences represented by Sequence ID No. 1 to 109, or a nucleotide sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides. (d) Polynucleotides containing a nucleotide sequence complementary to any of the nucleotide sequences represented by Sequence ID No. 1 to 109 or a nucleotide sequence in which u is t, variants thereof, derivatives thereof, or fragments thereof containing 15 or more consecutive nucleotides, (e) A polynucleotide that hybridizes with any of the polynucleotides described in (a) to (d) above under stringent conditions.

[0507] These polynucleotides (a) to (e) consist of or are derived from any of the base sequences represented by SEQ ID NOs: 1 to 109.

[0508] The nucleic acids usable in the present invention, such as nucleic acid probes or primers, may further include, in addition to at least one polynucleotide selected from the group consisting of polynucleotides (a) to (e) above, at least one polynucleotide selected from the group consisting of polynucleotides (f) to (j) below: (f) A polynucleotide consisting of a base sequence represented by any of sequence numbers 110 to 200, or a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases. (g) Polynucleotides containing a base sequence represented by any of SEQ ID NOs: 110-200, variants thereof, derivatives thereof, or fragments thereof containing 15 or more consecutive bases. (h) A polynucleotide consisting of a nucleotide sequence represented by any of sequence numbers 110 to 200 or a nucleotide sequence complementary to the nucleotide sequence in said sequence where u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides. (i) A polynucleotide containing a nucleotide sequence represented by any of sequence numbers 110 to 200, or a nucleotide sequence complementary to the nucleotide sequence in said sequence where u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides, (j) A polynucleotide that hybridizes with any of the polynucleotides described in (f) to (i) above under stringent conditions.

[0509] These polynucleotides (f) to (j) consist of or are derived from the base sequence represented by any of the sequence numbers 110 to 200.

[0510] The nucleic acid used in this invention may be DNA or RNA.

[0511] The nucleic acids usable in this invention can be produced using common techniques such as DNA recombination, PCR, and automated DNA / RNA synthesizer methods. Examples of DNA recombination and PCR techniques include those described in Ausubel et al., *Current Protocols in Molecular Biology*, John Willey & Sons, US (1993); and Sambrook et al., *Molecular Cloning: A Laboratory Manual*, Cold Spring Harbor Laboratory Press, US (1989).

[0512] Human-derived hsa-miR-3131, hsa-miR-6757-5p, hsa-miR-4706, hsa-miR-5001-5p, hsa-miR-3180-3p, hsa-miR-642b-3p, hsa-miR-4655-5p, hsa-miR-6819-5p, hsa-miR-937-5p, hsa-miR-4688, hsa-miR-6741-5p, hsa-miR-7107-5p, hsa-miR-4271, hsa-miR-1229-5p, hsa-miR-4707-5p, hsa-miR-6808-5p, hsa-miR-4656, hsa-miR-6076, hsa-miR-6762-5p, hsa-miR-7109-5p, hsa-miR-6732-5p, hsa-miR-3195, hsa-miR-7150, hsa-miR-642a-3p, hsa-miR-1249-5p, hsa-miR-3185, hsa-miR-4689, hsa-miR-3141, hsa-miR-6840-3p, hsa-miR-3135b, hsa-miR-1914-3p, hsa-miR-4446-3p, hsa-miR-4433b-3p, hsa-miR-6877-5p, hsa-miR-6848-5p, hsa-miR-3620-5p, hsa-miR-6825-5p, hsa-miR-5739, hsa-miR-3663-3p, hsa-miR-4695-5p, hsa-miR-3162-5p, hsa-miR-3679-5p, hsa-miR-8059, hsa-miR-7110-5p, hsa-miR-1275, hsa-miR-6779-5p, hsa-miR-197-5p, hsa-miR-6845-5p, hsa-miR-4327, hsa-miR-4723-5p, hsa-miR-4530, hsa-miR-6771-5p, hsa-miR-614, hsa-miR-92a-2-5p, hsa-miR-6891-5p, hsa-miR-6124, hsa-miR-4687-3p, hsa-miR-4442, hsa-miR-7977, hsa-miR-6785-5p, hsa-miR-4497, hsa-miR-8071, hsa-miR-663b, hsa-miR-3180, hsa-miR-4251, which consist of nucleotide sequences represented by SEQ ID NOs: 1 to 200hsa-miR-1285-3p, hsa-miR-6870-5p, hsa-miR-4484, hsa-miR-4476, hsa-miR-6749-5p, hsa-miR-4454, hsa-miR-6893-5p, hsa-miR-6085, hsa-miR- 4787-5p, hsa-miR-149-3p, hsa-miR-7704, hsa-miR-6125, hsa-miR-6090, hsa-miR-3197, hsa-miR-6850-5p, hsa-miR-4467, hsa-miR-6885-5p, hsa-m iR-6803-5p, hsa-miR-6798-5p, hsa-miR-6780b-5p, hsa-miR-6768-5p, hsa-miR-5100, hsa-miR-6724-5p, hsa-miR-6879-5p, hsa-miR-7108-5p, hsa -miR-4649-5p, hsa-miR-4739, hsa-miR-6089, hsa-miR-1908-5p, hsa-miR-4516, hsa-miR-2861, hsa-miR-4492, hsa-miR-4294, hsa-miR-6791-5p, hs a-miR-1469, hsa-miR-6752-5p, hsa-miR-4730, hsa-miR-6126, hsa-miR-6869-5p, hsa-miR-1268a, hsa-miR-6799-5p, hsa-miR-8069, hsa-miR-3621 hsa-miR-4763-3p hsa-miR-1228-5p hsa-miR-760 hsa-miR-187-5p hsa-miR-7111-5p hsa-miR-6088 hsa-miR-6805-3p hsa-miR-4640-5p hsa- miR-6721-5p, hsa-miR-6880-5p, hsa-miR-711, hsa-miR-128-1-5p, hsa-miR-4525, hsa-miR-486-3p, hsa-miR-6756-5p, hsa-miR-1260b, hsa-miR-3 184-5p, hsa-miR-6075, hsa-miR-204-3p, hsa-miR-4728-5p, hsa-miR-4534, hsa-miR-4758-5p, hsa-miR-8063, hsa-miR-6836-3p, hsa-miR-6789-5phsa-miR-744-5p, hsa-miR-1909-3p, hsa-miR-887-3p, hsa-miR-4745-5p, hsa-miR-4433a-3p, hsa-miR-5090, hsa-miR-296-5p, hsa-miR-939-5p, hsa-miR-3648, hsa-miR-3196, hsa-miR-6722-3p, hsa-miR-6805-5p, hsa-miR-1202, hsa-miR-6775-5p, hsa-miR-6087, hsa-miR-6765-5p, hsa-miR-6875-5p, hsa-miR-4674, hsa-miR-1233-5p, hsa-miR-7114-5p, hsa-miR-5787, hsa-miR-8072, hsa-miR-3619-3p, hsa-miR-4632-5p, hsa-miR-6800-5p, hsa-miR-4634, hsa-miR-4486, hsa-miR-6727-5p, hsa-miR-4505, hsa-miR-4725-3p, hsa-miR-1538, hsa-miR-320b, hsa-miR-1915-5p, hsa-miR-328-5p, hsa-miR-6820-5p, hsa-miR-6726-5p, hsa-miR-3665, hsa-miR-638, hsa-miR-762, hsa-miR-4466, hsa-miR-3940-5p, hsa-miR-1237-5p, hsa-miR-575, hsa-miR-3656, hsa-miR-4488, hsa-miR-4281, hsa-miR-6781-5p, hsa-miR-4532, hsa-miR-4665-5p, hsa-miR-6816-5p, hsa-miR-4508, hsa-miR-6784-5p, hsa-miR-6786-5p, hsa-miR-4741, hsa-miR-1343-5p, hsa-miR-1227-5p, hsa-miR-4734, hsa-miR-3960, hsa-miR-128-2-5p, hsa-miR-6743-5p, hsa-miR-663a, hsa-miR-6729-5p, hsa-miR-1915-3p, hsa-miR-1268b, hsa-miR-4651, hsa-miR-3178 and hsa-miR-4463 are known,As mentioned above, the method for obtaining it is also known. Therefore, based on the base sequence of this miRNA / gene, nucleic acids usable in the present invention, such as polynucleotides as nucleic acid probes or primers, can be produced.

[0513] Such nucleic acids, such as nucleic acid probes or primers, can be chemically synthesized using automated nucleic acid synthesizers. The phosphoamidite method is generally used for this synthesis, and this method allows for the automated synthesis of single-stranded DNA up to approximately 100 base pairs. Automated nucleic acid synthesizers are commercially available from companies such as Polygen, ABI, and Applied BioSystems.

[0514] Alternatively, the polynucleotides of the present invention can also be produced by cDNA cloning. For cDNA cloning technology, for example, the microRNA Cloning Kit Wako can be used.

[0515] The sequences of nucleic acids, such as nucleic acid probes and primers, used to detect polynucleotides consisting of a base sequence represented by any of SEQ ID NOs: 1 to 200, may not exist in the body as miRNA or its precursor. For example, the base sequences represented by SEQ ID NOs: 166 and 196 are generated from a precursor represented by SEQ ID NOs: 379, but this precursor has a hairpin-like structure as shown in Figure 1, and the base sequences represented by SEQ ID NOs: 166 and 196 have mismatched sequences. Therefore, a base sequence that is perfectly complementary to the base sequence represented by SEQ ID NOs: 166 or 196 will not be naturally generated in the body. Thus, nucleic acids, such as nucleic acid probes and primers, used to detect a base sequence represented by any of SEQ ID NOs: 1 to 200 may have artificial base sequences that do not exist in the body.

[0516] 3. Kits or devices for detecting hippocampal atrophy The present invention provides a hippocampal atrophy detection kit or device for measuring target nucleic acids that are hippocampal atrophy markers, comprising one or more hippocampal atrophy detection nucleic acids according to the present invention, such as one or more polynucleotides that can be used as nucleic acid probes or primers.

[0517] The target nucleic acid, which is a hippocampal atrophy marker in the present invention, is preferably selected from at least one of the following group A. Group A: miR-3131, miR-6757-5p, miR-4706, miR-5001-5p, miR-3180-3p, miR-642b-3p, miR-4655-5p, miR-6819-5p, miR-937-5p, miR-4688, miR-6741-5p, mi R-7107-5p, miR-4271, miR-1229-5p, miR-4707-5p, miR-6808-5p, miR-4656, miR-6076, miR-6762-5p, miR-7109-5p, miR-6732-5p, miR-3195, miR-71 50, miR-642a-3p, miR-1249-5p, miR-3185, miR-4689, miR-3141, miR-6840-3p, miR-3135b, miR-1914-3p, miR-4446-3p, miR-4433b-3p, miR-6877-5p miR-6848-5p miR-3620-5p miR-6825-5p miR-5739 miR-3663-3p miR-4695-5p miR-3162-5p miR-3679-5p miR-8059 miR-7110-5p miR-1275 miR-6779-5p, miR-197-5p, miR-6845-5p, miR-4327, miR-4723-5p, miR-4530, miR-6771-5p, miR-614, miR-92a-2-5p, miR-6891-5p, miR-6124, miR-4 687-3p, miR-4442, miR-7977, miR-6785-5p, miR-4497, miR-8071, miR-663b, miR-3180, miR-4251, miR-1285-3p, miR-6870-5p, miR-4484, miR-4476 miR-6749-5p, miR-4454, miR-6893-5p, miR-6085, miR-4787-5p, miR-149-3p, miR-7704, miR-6125, miR-6090, miR-3197, miR-6850-5p, miR-4467, mi R-6885-5p, miR-6803-5p, miR-6798-5p, miR-6780b-5p, miR-6768-5p, miR-5100, miR-6724-5p, miR-6879-5p, miR-7108-5p, miR-4649-5p, miR-4739miR-6089, miR-1908-5p, miR-4516, miR-2861, miR-4492, miR-4294, miR-6791-5p, miR-1469, miR-6752 -5p, miR-4730, miR-6126, miR-6869-5p, miR-1268a, miR-6799-5p, miR-8069, miR-3621 and miR-4763-3p,

[0518] In addition to the target nucleic acids selected from Group A, additional target nucleic acids that may be used for measurement are selected from Group B below. Group B: miR-1228-5p, miR-760, miR-187-5p, miR-7111-5p, miR-6088, miR-6805-3p, miR-4640-5p, miR-6721-5p, miR-6880-5p, miR-711, miR-128-1-5p, miR-4525, miR-486-3p, miR-6756-5p, miR-1260b, miR-3184-5p, miR-6075, miR-204-3p, miR-4728-5p, miR-4534, miR-4758-5p, miR-8063, miR-6836-3p, miR-6789-5p, miR-744-5p, miR-1909-3p, miR-887-3p, miR-4745-5p, miR-4433a-3p, miR-5090, miR-296-5p, miR-939-5p, miR-3648, miR-3196, miR-6722-3p, miR-6805-5p, miR-1202, miR-6775-5p, miR-6087, miR-6765-5p, miR-6875-5p, miR-4674, miR-1233-5p, miR-7114-5p, miR-5787, miR-8072, miR-3619-3p, miR-4632-5p, miR-6800-5p, miR-4634, miR-4486, miR-6727-5p, miR-4505, miR-4725-3p, miR-1538, miR-320b, miR-1915-5p, miR-328-5p, miR-6820-5p, miR-6726-5p, miR-3665, miR-638, miR-762, miR-4466, miR-3940-5p, miR-1237-5p, miR-575, miR-3656, miR-4488, miR-4281, miR-6781-5p, miR-4532, miR-4665-5p, miR-6816-5p, miR-4508, miR-6784-5p, miR-6786-5p, miR-4741, miR-1343-5p, miR-1227-5p, miR-4734, miR-3960, miR-128-2-5p, miR-6743-5p, miR-663a, miR-6729-5p, miR-1915-3p, miR-1268b, miR-4651, miR-3178 and miR-4463

[0519] The kit or device of the present invention comprises a target nucleic acid that is a hippocampal atrophy marker or a complementary strand of said polynucleotide, and one or more polynucleotides or variants thereof selected from the polynucleotides that are specifically bindable nucleic acids, preferably the miRNAs listed in the above group.

[0520] When the above-mentioned target nucleic acids are compared with samples from normal individuals whose hippocampus is not atrophied (hereinafter also referred to as "subjects (test subjects)" or "individuals with non-hippocampal atrophy"), the expression levels of these target nucleic acids increase or decrease (hereinafter referred to as "increase / decrease") in samples from patients with hippocampal atrophy (hereinafter also referred to as "patients with hippocampal atrophy," "subjects (test subjects)," or "individuals with hippocampal atrophy"), depending on the type of target nucleic acid. The kit or device of the present invention can be effectively used to detect hippocampal atrophy by measuring the expression levels of the above-mentioned target nucleic acids in body fluids from subjects to be tested for hippocampal atrophy, for example, subjects suspected of having hippocampal atrophy (e.g., humans) and body fluids from subjects with non-hippocampal atrophy, and comparing them.

[0521] The kit or device of the present invention may include at least one nucleic acid for detecting hippocampal atrophy, such as a nucleic acid probe or primer.

[0522] In one embodiment, the kit or device of the present invention may include at least one polynucleotide comprising (or consisting of) a nucleotide sequence represented by any of SEQ ID NOs: 1 to 109, or a nucleotide sequence in which u is t; a polynucleotide comprising (or consisting of) a complementary sequence thereof; a polynucleotide that hybridizes with those polynucleotides under stringent conditions; or a variant or fragment comprising 15 or more consecutive nucleotides of those polynucleotide sequences.

[0523] In one embodiment, the kit or device of the present invention may further include one or more polynucleotides comprising (or consisting of) a nucleotide sequence represented by any of SEQ ID NOs: 110 to 200, or a nucleotide sequence in which u is t; polynucleotides comprising (or consisting of) a complementary sequence thereof; polynucleotides that hybridize with those polynucleotides under stringent conditions; or variants or fragments comprising 15 or more consecutive nucleotides of those polynucleotide sequences.

[0524] In one embodiment, the fragments that can be included in the kit or device of the present invention are, for example, one or more, preferably two or more polynucleotides selected from the group consisting of (1) and (2) below. (1) A polynucleotide containing 15 or more consecutive base sequences in a base sequence where u is t, or in a complementary sequence thereof, in any of the base sequences represented by Sequence ID No. 1 to 109. (2) A polynucleotide containing 15 or more consecutive base sequences in a base sequence in which u is t, or in a complementary sequence thereof, as represented by any of sequence numbers 110 to 200.

[0525] In one embodiment, the polynucleotide is a polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 1 to 109 or a base sequence in which u is t, a polynucleotide consisting of a complementary sequence thereof, a polynucleotide that hybridizes with those polynucleotides under stringent conditions, or a variant thereof containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive base sequences.

[0526] In one embodiment, the polynucleotide is a polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 110 to 200 or a base sequence in which u is t, a polynucleotide consisting of a complementary sequence thereof, a polynucleotide that hybridizes with those polynucleotides under stringent conditions, or a variant thereof containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.

[0527] In a preferred embodiment, the fragment may be a polynucleotide containing 15 or more, preferably 17 or more, and more preferably 19 or more consecutive bases.

[0528] In the present invention, the size of the polynucleotide fragment is such that, in the base sequence of each polynucleotide, the number of consecutive bases is in the range of, for example, 15 to less than the total number of bases in the sequence, 17 to less than the total number of bases in the sequence, 19 to less than the total number of bases in the sequence, and so on.

[0529] The kit or device of the present invention may contain one nucleic acid (polynucleotide) that specifically binds to the above-mentioned hippocampal atrophy marker (target nucleic acid) polynucleotide or the complementary chain of said polynucleotide, or it may contain a combination of two or more such nucleic acids.

[0530] The combination of polynucleotides included in the kit or device of the present invention that can specifically bind to a target nucleic acid is, specifically, one, two, three, four, five, six, seven, eight, nine, ten or more of the above polynucleotides consisting of or derived from the base sequences represented by SEQ ID NOs: 1 to 740 shown in Table 1 (for example, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24) Examples include combinations of numbers such as 1, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 70 or more, 80 or more, 90 or more, or 100 or more. However, these are merely examples, and all other possible combinations are included in the present invention.

[0531] In one embodiment, the target nucleic acid of the nucleic acid (e.g., nucleic acid probe or primer) included in the kit or device of the present invention is at least one polynucleotide selected from the hippocampal atrophy markers of group A above (e.g., miR-3131, miR-6757-5p, miR-4706, miR-5001-5p, miR-3180-3p, miR-642b-3p, miR-4655-5p, miR-6819-5p, miR-937-5p, miR-4688, miR-6741-5p, miR-7107-5p, miR-4271, miR-1229-5 p, miR-4707-5p, miR-6808-5p, miR-4656, miR-6076, miR-6762-5p, miR-7109-5p, miR-6732-5p, miR-3195, miR-7150, miR-642a-3p, miR-1249-5p, miR -3185, miR-4689, miR-3141, miR-6840-3p, miR-3135b, miR-1914-3p, miR-4446-3p, miR-4433b-3p, miR-6877-5p, miR-6848-5p, miR-3620-5p, miR-68 25-5p, miR-5739, miR-3663-3p, miR-4695-5p, miR-3162-5p, miR-3679-5p, miR-8059, miR-7110-5p, miR-1275, miR-6779-5p, miR-197-5p, miR-6845 -5p, miR-4327, miR-4723-5p, miR-4530, miR-6771-5p, miR-614, miR-92a-2-5p, miR-6891-5p, miR-6124, miR-4687-3p, miR-4442, miR-7977, miR-678 5-5p, miR-4497, miR-8071, miR-663b, miR-3180, miR-4251, miR-1285-3p, miR-6870-5p, miR-4484, miR-4476, miR-6749-5p, miR-4454, miR-6893-5p, miR-6085, miR-4787-5p, miR-149-3p, miR-7704, miR-6125, miR-6090, miR-3197, miR-6850-5p, miR-4467, miR-6885-5p, miR-6803-5p, miR-6798-5p,miR-6780b-5p, miR-6768-5p, miR-5100, miR-6724-5p, miR-6879-5p, miR-7108-5p, miR-4649-5p, miR-4739, m iR-6089, miR-1908-5p, miR-4516, miR-2861, miR-4492, miR-4294, miR-6791-5p, miR-1469, miR-6752-5p, miR The selected polynucleotide may be a combination of the following: miR-4730, miR-6126, miR-6869-5p, miR-1268a, miR-6799-5p, miR-8069, miR-3621, or miR-4763-3p polynucleotides, or any combination of two or more of these, and at least one polynucleotide selected from the hippocampal atrophy markers of Group A, excluding the selected polynucleotide. In another embodiment, the target nucleic acid of the nucleic acid (e.g., nucleic acid probe or primer) included in the kit or device of the present invention may be a combination of at least one polynucleotide selected from the hippocampal atrophy markers of Group A, at least one polynucleotide selected from the hippocampal atrophy markers of Group A, excluding the selected polynucleotide, and at least one polynucleotide selected from the hippocampal atrophy markers of Group B. In yet another embodiment, the target nucleic acid (e.g., nucleic acid probe or primer) included in the kit or device of the present invention may be a combination of at least one polynucleotide selected from the hippocampal atrophy markers of group A and at least one polynucleotide selected from the hippocampal atrophy markers of group B. In one embodiment, the target nucleic acid in the kit or device of the present invention may be a combination of at least one polynucleotide selected from the hippocampal atrophy markers of group A and at least one polynucleotide selected from the group consisting of the hippocampal atrophy markers of group A and the hippocampal atrophy markers of group B, excluding the selected polynucleotide.

[0532] One embodiment, for example, relates to a kit or device for distinguishing individuals with hippocampal atrophy from those without, in the present invention, and it is desirable that the combination of hippocampal atrophy markers (target nucleic acids) be a combination of two or more polynucleotides consisting of the base sequences shown in SEQ ID NOs.1 to 740 in Table 1. The combination of hippocampal atrophy markers (target nucleic acids) is a combination of two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more (for example, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, It is also preferable that the combinations be 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 70 or more, 80 or more, 90 or more, or 100 or more.

[0533] Specifically, as a hippocampal atrophy marker (target nucleic acid), any two or more of the above polynucleotides consisting of the base sequences represented by SEQ ID NOs: 1 to 200 can be combined. Preferably, this combination includes at least one polynucleotide selected from the group of polynucleotides consisting of the base sequences represented by SEQ ID NOs: 1 to 109, which have been newly discovered as hippocampal atrophy markers.

[0534] In one embodiment, with respect to a kit or device for distinguishing individuals with hippocampal atrophy from those without, it is desirable to combine any two of the above polynucleotides consisting of the base sequences represented by SEQ ID NOs: 1-3, 68, 110, 111, 114, 127, 135, 137, 142, 149, 152, and 155, or a corresponding miRNA or human miRNA, as the hippocampal atrophy marker (target nucleic acid) combination. It is preferable that the combination includes at least one polynucleotide selected from the group of polynucleotides consisting of the base sequences represented by SEQ ID NOs: 1-3 and 68, which have been newly discovered as hippocampal atrophy markers, or a corresponding miRNA or human miRNA.

[0535] In one embodiment, with respect to a kit or device for distinguishing between individuals with hippocampal atrophy and those without, it is desirable to combine any two of the above polynucleotides consisting of the base sequences represented by SEQ ID NOs: 1, 26, 65, 66, 71, 110, 112, 114, 125-127, 162, and 164-166, or a corresponding miRNA or human miRNA, as the hippocampal atrophy marker (target nucleic acid) combination. It is preferable that the combination includes at least one polynucleotide selected from the group of polynucleotides consisting of the base sequences represented by the newly discovered SEQ ID NOs: 1, 26, 65, 66, and 71, or a corresponding miRNA or human miRNA.

[0536] In one embodiment, relating to a kit or device for distinguishing individuals with hippocampal atrophy from those without, the present invention provides a combination of hippocampal atrophy markers (target nucleic acids) such as SEQ ID NOs: 1-7, 9-14, 16-21, 23-26, 30-32, 34, 35, 37-48, 50-56, 58-63, 67-73, 75, 77-93, 95-106, 108-111, 113-121, 124, 125 It is preferable to combine any two of the above polynucleotides, which consist of the base sequences represented in 127-129, 132-138, 140-143, 145, 146, 148-150, 152-155, 159-161, 163, 167-169, 171, 172, 174-189, 191-194, and 196-200, with their corresponding miRNA or human miRNA. The combination preferably includes at least one polynucleotide selected from the group of polynucleotides consisting of base sequences represented by SEQ ID NOs: 1-7, 9-14, 16-21, 23-26, 30-32, 34, 35, 37-48, 50-56, 58-63, 67-73, 75, 77-93, 95-106, and 108-109, which have been newly discovered as hippocampal atrophy markers, or a corresponding miRNA or human miRNA.

[0537] In one embodiment, relating to a kit or device for distinguishing individuals with hippocampal atrophy from those without, the present invention provides a combination of hippocampal atrophy markers (target nucleic acids) such as SEQ ID NOs: 1-5, 9, 10, 12, 13, 16-18, 20, 21, 24-26, 29-32, 37-39, 41, 42, 44, 45, 47-59, 61-63, 67-71, 73-75, 77-88, 90-94, 96-102, 104-111, 1 It is preferable to combine any two of the above polynucleotides, which consist of the base sequences represented at 13, 114, 117, 118, 121, 123, 125, 127, 128, 133-138, 141-143, 145-150, 152-159, 161-163, 167-169, 171-180, 182, 183, 185-194, and 196-200, with their corresponding miRNA or human miRNA. The combination preferably includes at least one polynucleotide selected from the group of polynucleotides consisting of base sequences represented by the newly discovered hippocampal atrophy markers SEQ ID NOs: 1-5, 9, 10, 12, 13, 16-18, 20, 21, 24-26, 29-32, 37-39, 41, 42, 44, 45, 47-59, 61-63, 67-71, 73-75, 77-88, 90-94, 96-102, and 104-109, or a corresponding miRNA or human miRNA.

[0538] In one embodiment, with respect to a kit or device for distinguishing hippocampal atrophy patients from non-hippocampal atrophy patients in the present invention, it is desirable to combine any two of the above polynucleotides consisting of the base sequences represented by SEQ ID NOs: 155, 188, 127, 5, 198, 189, 110, 176, 143, 102, 148, 101, 75, 109, 199, 145, 54, 174, 106, 152, 133, 2, 20, 51, and 114, or the corresponding miRNA or human miRNA, as the hippocampal atrophy marker (target nucleic acid) combination. It is preferable that the combination includes at least one polynucleotide selected from the group of polynucleotides consisting of the base sequences represented by SEQ ID NOs: 2, 5, 20, 51, 54, 75, 101, 102, 106, and 109, which have been newly discovered as hippocampal atrophy markers, or the corresponding miRNA or human miRNA.

[0539] In one embodiment, the present invention relates to a kit or device for distinguishing individuals with hippocampal atrophy from those without, and the combination of hippocampal atrophy markers (target nucleic acids) is as follows: SEQ ID NOs: 1-6, 9, 17, 21, 27, 34, 39, 43, 47-48, 51, 53-54, 59, 61-63, 71, 73-78, 80, 82-88, 90-92, 94, 96-98, 100, 102, 104, 106, 109-110, 113-114, 12 It is preferable to combine any two of the above polynucleotides, which consist of the base sequences represented at 1, 123-125, 127, 131-133, 135-137, 142-143, 145, 147-150, 152-153, 155, 159-162, 168-169, 174-176, 179, 182, 185, 187-189, 192-193, and 196-200, with their corresponding miRNAs or human miRNAs. The combination preferably includes at least one polynucleotide selected from the group of polynucleotides consisting of base sequences represented by SEQ ID NOs: 1-6, 9, 17, 21, 27, 34, 39, 43, 47-48, 51, 53-54, 59, 61-63, 71, 73-78, 80, 82-88, 90-92, 94, 96-98, 100, 102, 104, 106, and 109, which have been newly discovered as hippocampal atrophy markers, or a corresponding miRNA or human miRNA.

[0540] The number of polynucleotide combinations, which are hippocampal atrophy markers (target nucleic acids) used to distinguish the above-mentioned hippocampal atrophy, can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more (for example, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24). It may be any of the following: 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, or 70 or more, 80 or more, 90 or more, or 100 or more. Preferably, it is a combination of two or more.

[0541] Below, as a non-limiting example of the combination of hippocampal atrophy markers (target nucleic acids) used in the present invention, a combination of a polynucleotide consisting of the base sequence represented by Sequence ID No. 110 and a polynucleotide of a hippocampal atrophy marker selected from Tables 3 to 6 is given. The combination of hippocampal atrophy markers (target nucleic acids) may also be a combination of miRNA or human miRNA corresponding to the following combinations. (1) Combination of sequence numbers 110 and 114 (2) Combination of sequence numbers 110, 114, and 1 (3) Combinations of sequence numbers 110, 114, and 135 (4) Combinations of sequence numbers 110, 114, and 155 (5) Combinations of sequence numbers 110, 114, and 137 (6) Combinations of sequence numbers 110, 114, 155, and 135 (7) Combinations of sequence numbers 110, 114, 137, and 111 (8) Combinations of sequence numbers 110, 114, 155, and 2 (9) Combinations of sequence numbers 110, 114, 142, and 2 (10) Combinations of sequence numbers 110, 114, 1, and 149 (11) Combinations of sequence numbers 110, 114, 1, and 135 (12) Combinations of sequence numbers 110, 114, 155, and 68 (13) Combinations of sequence numbers 110, 114, 2, and 135 (14) Combinations of sequence numbers 110, 114, 155, 135, and 2 (15) Combinations of sequence numbers 110, 114, 155, 137, and 2 (16) Combinations of sequence numbers 110, 114, 3, 2, and 142 (17) Combinations of sequence numbers 110, 114, 142, 135, and 3 (18) Combinations of sequence numbers 110, 114, 127, 1, and 149 (19) Combinations of sequence numbers 110, 114, 127, 1, and 135 (20) Combinations of sequence numbers 110, 114, 155, 68, and 152 (21) Combinations of sequence numbers 110, 114, 68, 135, and 2 (22) Combinations of sequence numbers 110, 114, 142, 1, and 2 (23) Combinations of sequence numbers 127, 1, 162, 114, and 110 (24) Combinations of sequence numbers 1, 126, 125, 114, and 110 (25) Combinations of sequence numbers 66, 110, 165, 65, 166, and 164 (26) Combinations of sequence numbers 66, 110, 165, 26, 112, and 114 (27) Combinations of sequence numbers 1, 110, 165, 65, 164, and 71

[0542] As a non-limiting example of the combination of hippocampal atrophy markers (target nucleic acids) used in the present invention, the following examples illustrate combinations of a polynucleotide consisting of the base sequence represented by Sequence ID No. 39 and a polynucleotide of a hippocampal atrophy marker selected from Tables 3 to 6. The combination of hippocampal atrophy markers (target nucleic acids) may also be a combination of miRNA or human miRNA corresponding to the following combinations. (1) Combinations of sequence numbers 155, 87, 188, 127, 85, 5, 1, 110, 193, 175, 118, 152, 133, 39, 159, 149, 150, 114 (2) Combinations of sequence numbers 115, 188, 127, 85, 1, 16, 110, 41, 24, 200, 26, 193, 175, 108, 152, 113, 39, 159, 114 (3) Combinations of sequence numbers 155, 188, 127, 146, 5, 1, 16, 110, 200, 101, 193, 175, 145, 125, 152, 111, 39, and 114 (4) Combinations of sequence numbers 155, 87, 188, 127, 85, 1, 183, 196, 14, 189, 110, 24, 101, 193, 175, 118, 178, 152, 39, 150, 114 (5) Combinations of sequence numbers 179, 155, 142, 188, 127, 146, 1, 189, 110, 4, 200, 193, 175, 118, 63, 152, 111, 180, 39, and 114 (6) Combinations of sequence numbers 87, 188, 127, 85, 5, 1, 16, 196, 14, 38, 110, 4, 200, 193, 175, 109, 145, 152, 39, 159, 149, and 114 (7) Combinations of sequence numbers 155, 87, 142, 188, 127, 85, 5, 1, 189, 154, 110, 41, 193, 175, 167, 10, 152, 111, 133, 39, 171, 150, 114 (8) Combinations of sequence numbers 179, 188, 127, 5, 16, 154, 110, 193, 175, 118, 100, 109, 10, 88, 152, 39, 91, 159, 149, 82, 104, 182, 114 (9) Combinations of sequence numbers 155, 188, 127, 1, 183, 187, 110, 185, 86, 193, 175, 109, 145, 88, 3, 120, 152, 133, 39, 149, 182, and 114 (10) Combinations of sequence numbers 155, 87, 142, 188, 127, 85, 1, 16, 110, 26, 193, 175, 118, 97, 174, 152, 111, 133, 113, 39, 159, 114 (11) Combinations of sequence numbers 155, 87, 188, 127, 1, 110, 9, 24, 200, 193, 43, 109, 145, 125, 178, 135, 174, 152, 133, 39, 91, 149, 182, 114 (12) Combinations of sequence numbers 155, 87, 127, 5, 1, 198, 189, 110, 41, 200, 193, 175, 75, 31, 109, 59, 174, 152, 111, 133, 113, 39, 91, 114 (13) Combinations of sequence numbers 155, 87, 188, 127, 5, 1, 16, 187, 110, 176, 193, 175, 145, 125, 88, 152, 89, 141, 133, 39, 149, 150, 114 (14) Combinations of sequence numbers 179, 95, 188, 127, 85, 5, 129, 16, 196, 154, 110, 200, 193, 175, 118, 63, 174, 108, 113, 39, 91, 159, 34, and 114 (15) Combinations of sequence numbers 155, 87, 188, 127, 85, 5, 1, 16, 196, 198, 38, 110, 24, 200, 193, 88, 96, 152, 111, 39, 159, 149, 182, 114 (16) Combinations of sequence numbers 179, 121, 155, 87, 188, 127, 5, 187, 14, 189, 194, 110, 58, 200, 193, 118, 145, 125, 59, 152, 111, 113, 39, 159, 149, 114 (17) Combinations of sequence numbers 121, 155, 87, 188, 127, 1, 189, 67, 110, 4, 176, 193, 75, 145, 125, 88, 59, 108, 152, 111, 39, 159, 149, 182, 114, and 23 (18) Combinations of sequence numbers 155, 137, 87, 168, 188, 196, 189, 110, 41, 4, 24, 58, 101, 193, 175, 145, 152, 111, 113, 39, 91, 61, 51, 55, 182, 114 (19) Combinations of sequence numbers 155, 87, 188, 127, 85, 1, 16, 84, 187, 110, 4, 26, 193, 175, 118, 109, 88, 108, 152, 111, 39, 159, 149, 182, 114 (20) Combinations of sequence numbers 179, 155, 132, 168, 188, 127, 5, 1, 14, 189, 110, 124, 4, 24, 200, 193, 175, 97, 145, 174, 108, 152, 133, 39, 114 (21) Combinations of sequence numbers 142, 188, 85, 146, 1, 196, 187, 189, 110, 58, 101, 193, 175, 25, 105, 54, 120, 152, 111, 113, 39, 91, 159, 149, 61, 182, 114 (22) Combinations of sequence numbers 121, 155, 95, 188, 127, 80, 198, 189, 110, 200, 101, 193, 175, 75, 145, 88, 120, 152, 133, 39, 91, 149, 34, 171, 140, 150, 114 (23) Combinations of sequence numbers 155, 188, 127, 85, 1, 16, 196, 84, 53, 189, 110, 4, 68, 101, 193, 145, 178, 54, 108, 152, 111, 133, 39, 159, 182, 114 (24) Combinations of sequence numbers 121, 115, 155, 137, 188, 127, 5, 1, 196, 35, 187, 110, 193, 175, 118, 97, 178, 48, 37, 152, 133, 39, 91, 149, 182, 114 (25) Combinations of sequence numbers 155, 87, 188, 127, 85, 1, 16, 196, 187, 110, 24, 200, 185, 101, 175, 118, 192, 145, 88, 54, 108, 152, 133, 39, 91, 149, 182, 114 (26) Combinations of sequence numbers 115, 155, 87, 188, 127, 146, 5, 16, 161, 53, 198, 110, 143, 148, 193, 175, 25, 100, 109, 97, 48, 108, 152, 133, 39, 149, and 114 (27) Combinations of sequence numbers 155, 87, 142, 188, 85, 1, 16, 196, 53, 110, 9, 41, 4, 185, 193, 175, 97, 135, 174, 73, 152, 111, 133, 113, 39, 149, 55, 182, 114 (28) Combinations of sequence numbers 121, 155, 188, 127, 85, 1, 16, 198, 189, 110, 4, 86, 101, 193, 75, 199, 145, 108, 152, 111, 113, 39, 7, 91, 159, 149, 182, 114 (29) Combinations of sequence numbers 155, 142, 188, 127, 5, 129, 16, 14, 154, 110, 153, 193, 175, 118, 75, 109, 169, 97, 21, 10, 59, 152, 111, 133, 39, 149, 18, 114 (30) Combinations of sequence numbers 179, 155, 188, 127, 5, 196, 187, 14, 189, 154, 38, 110, 101, 175, 118, 25, 100, 174, 120, 108, 152, 133, 39, 91, 159, 149, 82, 104, 182, 114 (31) Combinations of sequence numbers 155, 188, 127, 79, 16, 198, 110, 68, 200, 102, 193, 175, 43, 100, 109, 167, 10, 59, 191, 152, 111, 133, 39, 159, 149, 82, 55, 182, 114 (32) Combinations of sequence numbers 155, 95, 87, 188, 127, 85, 1, 196, 198, 187, 189, 110, 200, 193, 175, 192, 109, 97, 145, 125, 59, 152, 133, 113, 39, 159, 149, 150, 114 (33) Combinations of sequence numbers 121, 155, 188, 127, 1, 198, 187, 189, 154, 110, 193, 175, 118, 31, 109, 145, 59, 54, 174, 108, 152, 133, 113, 39, 91, 159, 149, 2, 55, 182, 114 (34) Combinations of sequence numbers 121, 155, 87, 188, 127, 85, 1, 79, 16, 196, 187, 110, 176, 24, 101, 193, 175, 109, 199, 145, 178, 88, 152, 111, 133, 39, 149, 150, 182, 114, 23 (35) Combinations of sequence numbers 155, 188, 127, 1, 196, 189, 110, 32, 41, 143, 185, 193, 175, 97, 145, 178, 54, 174, 108, 152, 111, 133, 39, 91, 149, 61, 18, 55, 182, 114 (36) Combinations of sequence numbers 121, 155, 95, 188, 127, 196, 53, 187, 189, 194, 110, 128, 101, 193, 175, 25, 109, 97, 145, 174, 152, 111, 113, 39, 91, 159, 149, 104, 182, 114 (37) Combinations of sequence numbers 155, 137, 168, 188, 127, 16, 196, 187, 154, 110, 6, 44, 9, 200, 148, 101, 193, 175, 109, 145, 178, 48, 152, 133, 113, 39, 77, 55, 182, 114 (38) Combinations of sequence numbers 155, 87, 188, 127, 85, 1, 16, 196, 84, 17, 14, 110, 176, 24, 200, 193, 175, 75, 109, 97, 145, 174, 108, 152, 141, 39, 159, 149, 182, 114 (39) Combinations of sequence numbers 155, 87, 188, 127, 85, 1, 16, 196, 14, 110, 176, 185, 193, 175, 118, 109, 199, 145, 48, 108, 152, 141, 133, 39, 159, 149, 55, 182, 114, and 23 (40) Combinations of sequence numbers 179, 121, 155, 95, 188, 127, 85, 1, 129, 196, 187, 110, 176, 193, 175, 31, 145, 178, 48, 88, 47, 54, 174, 120, 108, 133, 39, 91, 149, 114 (41) Combinations of sequence numbers 179, 115, 155, 87, 188, 127, 85, 146, 5, 1, 45, 84, 187, 189, 110, 128, 56, 200, 185, 86, 193, 175, 118, 145, 48, 59, 152, 113, 39, 159, 149, 114 (42) Combinations of sequence numbers 179, 95, 142, 188, 127, 5, 1, 129, 16, 187, 110, 193, 175, 118, 100, 109, 97, 125, 63, 92, 152, 133, 180, 39, 91, 159, 149, 104, 171, 150, 182, 114 (43) Combinations of sequence numbers 155, 137, 142, 188, 127, 85, 196, 189, 110, 136, 41, 143, 148, 193, 175, 118, 199, 97, 145, 178, 88, 117, 108, 133, 39, 91, 159, 149, 18, 182, 114 (44) Combinations of sequence numbers 13, 155, 137, 87, 188, 127, 85, 196, 187, 110, 136, 41, 24, 200, 101, 193, 175, 118, 97, 145, 48, 152, 111, 133, 113, 39, 91, 149, 55, 182, 114 (45) Combinations of sequence numbers 155, 188, 127, 85, 5, 1, 79, 84, 187, 67, 110, 41, 176, 175, 118, 109, 97, 145, 54, 108, 152, 111, 133, 113, 39, 91, 159, 149, 171, 182, and 114 (46) Combinations of sequence numbers 155, 87, 188, 127, 85, 146, 1, 16, 196, 187, 14, 110, 200, 26, 101, 193, 175, 97, 145, 48, 120, 108, 152, 141, 111, 39, 159, 149, 77, 182, 114 (47) Combinations of sequence numbers 155, 168, 188, 127, 85, 5, 1, 16, 196, 84, 187, 189, 110, 128, 136, 176, 200, 193, 175, 118, 109, 145, 125, 152, 89, 133, 39, 149, 46, 182, 114 (48) Combinations of sequence numbers 179, 121, 115, 155, 188, 127, 1, 16, 196, 161, 84, 67, 110, 124, 4, 176, 24, 148, 193, 175, 109, 145, 178, 48, 117, 152, 39, 159, 149, 182, 114 (49) Combinations of sequence numbers 115, 95, 87, 188, 127, 85, 5, 1, 16, 196, 198, 187, 110, 176, 101, 193, 175, 118, 109, 97, 125, 178, 120, 108, 152, 141, 39, 159, 149, 182, and 114 (50) Combinations of sequence numbers 179, 87, 188, 127, 85, 30, 1, 84, 198, 187, 110, 193, 175, 109, 145, 125, 54, 174, 120, 163, 152, 133, 113, 39, 91, 159, 149, 82, 55, 182, 114 (51) Combinations of sequence numbers 115, 155, 137, 168, 188, 127, 5, 1, 79, 196, 187, 189, 194, 110, 136, 193, 175, 118, 109, 199, 145, 88, 152, 133, 39, 91, 149, 18, 46, 182, 114 (52) Combinations of sequence numbers 121, 155, 188, 127, 85, 1, 196, 187, 110, 176, 24, 200, 26, 101, 193, 175, 118, 25, 100, 169, 145, 125, 178, 54, 92, 152, 111, 113, 39, 91, 159, 55, 114 (53) Combinations of sequence numbers 155, 95, 188, 127, 85, 1, 16, 196, 187, 189, 110, 136, 176, 69, 101, 193, 175, 118, 25, 75, 109, 97, 167, 145, 108, 152, 111, 39, 159, 149, 171, 182, 114 (54) Combinations of sequence numbers 121, 115, 155, 168, 188, 127, 85, 5, 1, 84, 198, 187, 14, 189, 110, 193, 109, 97, 145, 54, 120, 152, 111, 113, 39, 91, 159, 149, 104, 150, 182, 114, 12 (55) Combinations of sequence numbers 155, 188, 127, 85, 146, 5, 1, 80, 183, 196, 189, 110, 177, 193, 175, 109, 169, 97, 167, 145, 59, 174, 152, 111, 133, 39, 91, 149, 82, 103, 52, 114 (56) Combinations of sequence numbers 121, 168, 188, 127, 85, 16, 45, 198, 187, 189, 110, 4, 176, 200, 148, 86, 193, 175, 97, 145, 125, 174, 152, 113, 39, 91, 159, 149, 70, 82, 182, 114 (57) Combinations of sequence numbers 121, 155, 188, 127, 85, 5, 1, 129, 187, 194, 110, 176, 24, 86, 26, 193, 118, 100, 125, 54, 174, 120, 152, 133, 39, 91, 149, 104, 171, 150, 182, 114 (58) Combinations of sequence numbers 155, 142, 188, 127, 85, 1, 80, 183, 196, 187, 110, 124, 200, 101, 193, 25, 97, 145, 125, 59, 54, 174, 120, 108, 152, 133, 39, 91, 159, 82, 104, 61, 150, 114 (59) Combinations of sequence numbers 121, 155, 95, 87, 188, 127, 85, 16, 196, 187, 194, 110, 136, 176, 200, 185, 101, 193, 175, 109, 145, 59, 108, 152, 111, 113, 39, 91, 159, 149, 46, 55, 182, 114 (60) Combinations of sequence numbers 155, 87, 142, 188, 127, 85, 146, 5, 1, 16, 45, 196, 67, 110, 101, 193, 175, 118, 25, 109, 145, 178, 63, 54, 174, 108, 152, 39, 91, 159, 149, 55, 182, 114 (61) Combinations of sequence numbers 155, 188, 127, 85, 5, 1, 138, 196, 84, 187, 110, 24, 148, 177, 101, 193, 175, 100, 145, 178, 88, 54, 71, 152, 133, 39, 91, 149, 82, 61, 51, 55, 182, 114 (62) Combinations of sequence numbers 115, 155, 87, 168, 188, 127, 85, 1, 16, 196, 187, 110, 124, 41, 176, 24, 148, 153, 193, 175, 109, 145, 10, 88, 59, 120, 152, 133, 39, 91, 149, 2, 104, 182, 114 (63) Combinations of sequence numbers 87, 188, 127, 1, 79, 183, 196, 187, 189, 110, 6, 32, 24, 148, 86, 193, 175, 118, 100, 109, 88, 135, 108, 92, 152, 111, 113, 39, 149, 55, 150, 182, 114 (64) Combinations of sequence numbers 121, 155, 142, 188, 127, 85, 1, 16, 172, 53, 187, 110, 101, 193, 118, 75, 109, 199, 97, 145, 125, 63, 88, 54, 152, 42, 39, 159, 149, 82, 55, 114, 23 (65) Combinations of sequence numbers 155, 188, 127, 85, 146, 5, 1, 196, 84, 187, 110, 200, 193, 175, 118, 75, 97, 145, 125, 178, 59, 54, 106, 163, 152, 133, 39, 91, 159, 82, 34, 182, 114 (66) Combinations of sequence numbers 121, 95, 188, 127, 85, 5, 79, 84, 187, 189, 110, 4, 193, 175, 119, 25, 97, 145, 10, 88, 108, 152, 111, 133, 113, 39, 91, 159, 149, 171, 150, 182, 114 (67) Combinations of sequence numbers 115, 155, 188, 127, 85, 1, 16, 196, 161, 187, 189, 110, 176, 24, 101, 193, 175, 118, 31, 199, 145, 48, 54, 152, 111, 133, 39, 149, 82, 104, 51, 182, 114 (68) Combinations of sequence numbers 179, 13, 155, 87, 188, 127, 85, 1, 79, 183, 189, 110, 81, 24, 193, 175, 199, 167, 125, 88, 59, 174, 108, 152, 111, 113, 39, 159, 149, 70, 150, 114, and 23 (69) Combinations of sequence numbers 155, 87, 188, 127, 85, 1, 16, 196, 161, 84, 187, 14, 38, 124, 109, 145, 178, 48, 54, 96, 174, 120, 108, 152, 141, 39, 91, 159, 149, 82, 77, 55, 182, 93, 114 (70) Combinations of sequence numbers 155, 87, 168, 188, 127, 85, 1, 196, 187, 110, 136, 24, 200, 148, 193, 175, 118, 109, 178, 120, 108, 152, 111, 133, 39, 91, 159, 149, 82, 171, 18, 55, 182, 114 (71) Combinations of sequence numbers 155, 87, 142, 188, 127, 85, 80, 161, 84, 187, 189, 194, 110, 101, 193, 175, 25, 199, 97, 145, 120, 152, 111, 133, 39, 91, 159, 149, 103, 77, 184, 182, 114, and 23 (72) Combinations of sequence numbers 155, 95, 87, 188, 85, 5, 1, 196, 84, 53, 187, 110, 90, 176, 148, 193, 175, 118, 25, 145, 48, 88, 96, 174, 108, 152, 133, 39, 91, 149, 171, 55, 182, 114 (73) Combinations of sequence numbers 155, 95, 188, 127, 85, 146, 1, 45, 196, 187, 189, 194, 110, 128, 68, 200, 86, 177, 101, 193, 175, 118, 109, 199, 37, 92, 152, 133, 39, 159, 149, 104, 182, 114 (74) Combinations of sequence numbers 121, 155, 95, 168, 188, 127, 5, 16, 196, 172, 53, 187, 14, 189, 38, 67, 110, 68, 193, 175, 145, 178, 174, 152, 133, 39, 91, 159, 149, 82, 20, 182, 114, and 12 (75) Combinations of sequence numbers 95, 188, 127, 85, 1, 16, 196, 161, 14, 110, 32, 24, 175, 118, 100, 109, 97, 145, 178, 10, 59, 54, 108, 92, 111, 133, 180, 113, 39, 91, 159, 149, 184, 182, 114, and 40 (76) Combinations of sequence numbers 155, 95, 87, 142, 188, 127, 85, 5, 1, 196, 84, 198, 187, 110, 41, 68, 200, 177, 101, 193, 175, 118, 25, 109, 97, 145, 152, 111, 133, 113, 39, 159, 149, 55, 182, 114 (77) Combinations of sequence numbers 121, 155, 188, 127, 85, 1, 79, 16, 196, 187, 189, 110, 124, 193, 175, 75, 169, 97, 145, 178, 21, 63, 54, 108, 71, 152, 111, 133, 39, 91, 159, 149, 55, 114, 23 (78) Combinations of sequence numbers 121, 155, 188, 127, 85, 5, 1, 79, 160, 84, 187, 14, 110, 32, 176, 200, 193, 175, 118, 109, 97, 145, 178, 63, 10, 88, 152, 111, 133, 39, 91, 149, 77, 182, 114 (79) Combinations of sequence numbers 13, 155, 87, 168, 188, 127, 85, 196, 187, 189, 194, 110, 78, 24, 200, 177, 101, 193, 175, 118, 109, 125, 174, 108, 73, 152, 111, 133, 39, 159, 149, 171, 52, 182, 114 (80) Combinations of sequence numbers 121, 137, 142, 188, 127, 85, 5, 1, 196, 84, 187, 189, 38, 110, 4, 185, 177, 101, 193, 199, 145, 88, 3, 174, 152, 111, 133, 180, 113, 39, 91, 159, 149, 171, 140, 182, 114 (81) Combinations of sequence numbers 121, 95, 188, 127, 85, 5, 1, 196, 187, 189, 194, 110, 128, 4, 26, 177, 101, 193, 175, 31, 109, 97, 145, 62, 88, 108, 152, 111, 133, 39, 91, 159, 149, 82, 171, 182, 114 (82) Combinations of sequence numbers 121, 188, 127, 85, 30, 1, 16, 196, 187, 189, 11, 154, 194, 110, 58, 185, 101, 193, 175, 118, 25, 100, 88, 54, 152, 111, 180, 39, 91, 159, 61, 77, 20, 55, 182, 114, 23 (83) Combinations of sequence numbers 155, 87, 188, 127, 1, 138, 16, 196, 187, 154, 38, 110, 200, 101, 193, 175, 25, 100, 199, 145, 178, 96, 174, 92, 152, 111, 133, 113, 39, 91, 159, 149, 82, 77, 182, 114, 23 (84) Combinations of sequence numbers 87, 142, 188, 127, 85, 146, 5, 1, 196, 35, 189, 38, 67, 110, 9, 4, 177, 101, 193, 175, 118, 109, 145, 63, 88, 54, 108, 133, 39, 91, 159, 149, 72, 82, 51, 182, 114 (85) Combinations of sequence numbers 155, 137, 188, 127, 1, 16, 196, 161, 35, 187, 189, 38, 67, 110, 181, 200, 148, 101, 193, 175, 118, 109, 145, 125, 174, 120, 152, 141, 111, 133, 39, 91, 159, 82, 55, and 114 (86) Combinations of sequence numbers 155, 132, 87, 188, 127, 1, 196, 161, 53, 198, 187, 189, 110, 181, 136, 4, 176, 143, 200, 26, 193, 175, 75, 97, 145, 54, 174, 37, 163, 152, 111, 39, 70, 55, 182, 114 (87) Combinations of sequence numbers 179, 121, 155, 188, 127, 5, 1, 79, 16, 196, 187, 14, 67, 110, 176, 24, 143, 86, 175, 109, 145, 48, 88, 47, 54, 174, 120, 152, 133, 39, 91, 159, 149, 82, 182, 114 (88) Combinations of sequence numbers 121, 87, 142, 188, 127, 85, 45, 196, 187, 189, 194, 110, 176, 24, 102, 86, 101, 193, 118, 100, 109, 145, 88, 174, 108, 71, 99, 152, 141, 111, 133, 39, 91, 159, 149, 182, 114, 23 (89) Combinations of sequence numbers 121, 155, 87, 188, 127, 1, 16, 198, 187, 189, 38, 67, 194, 110, 4, 176, 24, 200, 185, 193, 175, 118, 192, 109, 167, 145, 125, 63, 120, 108, 152, 133, 180, 39, 91, 159, 149, 182 (90) Combinations of sequence numbers 121, 115, 155, 137, 168, 188, 127, 85, 1, 79, 138, 16, 196, 187, 67, 110, 136, 4, 101, 193, 175, 118, 109, 97, 145, 48, 54, 120, 108, 152, 133, 39, 91, 159, 149, 18, 182, 114 (91) Combinations of sequence numbers 137, 188, 127, 85, 146, 1, 16, 196, 161, 189, 110, 56, 58, 148, 193, 175, 118, 25, 100, 109, 145, 178, 48, 174, 120, 108, 152, 141, 133, 39, 91, 149, 82, 77, 55, 150, 114 (92) Combinations of sequence numbers 155, 87, 168, 188, 127, 85, 1, 196, 84, 189, 110, 124, 176, 24, 200, 185, 69, 175, 25, 169, 145, 125, 178, 96, 120, 117, 108, 152, 111, 133, 39, 91, 159, 149, 82, 182, 114 (93) Combinations of sequence numbers 155, 95, 188, 127, 85, 5, 1, 16, 187, 194, 110, 9, 41, 4, 153, 193, 175, 100, 109, 145, 62, 21, 48, 10, 54, 152, 111, 133, 39, 91, 197, 159, 149, 104, 171, 182, 114 (94) Combinations of sequence numbers 87, 188, 127, 85, 5, 1, 80, 196, 189, 154, 110, 124, 78, 186, 90, 177, 193, 175, 118, 31, 109, 97, 145, 88, 59, 54, 120, 108, 134, 152, 111, 133, 39, 91, 149, 104, 140, 182, 114 (95) Combinations of sequence numbers 179, 155, 95, 188, 127, 146, 5, 129, 16, 196, 84, 187, 14, 189, 110, 32, 68, 26, 193, 175, 109, 145, 178, 59, 54, 174, 120, 152, 133, 39, 91, 149, 82, 104, 61, 182, 93, 114, 23 (96) Combinations of sequence numbers 121, 115, 155, 87, 188, 127, 85, 1, 80, 161, 187, 14, 110, 4, 24, 200, 193, 109, 97, 145, 125, 178, 63, 54, 174, 152, 111, 133, 39, 91, 159, 149, 70, 82, 61, 55, 182, 114 (97) Combinations of sequence numbers 155, 137, 95, 87, 188, 127, 85, 146, 1, 196, 189, 38, 194, 110, 32, 176, 193, 175, 118, 109, 125, 178, 63, 59, 54, 96, 191, 174, 120, 152, 141, 133, 39, 91, 149, 82, 55, 182, 114 (98) Combinations of sequence numbers 179, 155, 87, 142, 188, 127, 85, 1, 80, 189, 110, 6, 56, 185, 153, 26, 193, 175, 109, 62, 178, 10, 88, 59, 135, 54, 108, 92, 152, 111, 133, 180, 113, 39, 91, 159, 149, 150, 114, 60 (99) Combinations of sequence numbers 179, 115, 188, 127, 85, 1, 79, 183, 196, 53, 187, 189, 194, 110, 200, 185, 193, 175, 119, 105, 97, 145, 125, 88, 54, 120, 152, 113, 39, 91, 116, 159, 149, 34, 61, 150, 182, 114, and 23 (100) Combinations of sequence numbers 87, 188, 127, 85, 16, 196, 84, 14, 189, 67, 110, 90, 24, 193, 175, 43, 100, 109, 145, 48, 63, 10, 88, 59, 54, 174, 108, 152, 111, 133, 39, 91, 159, 149, 82, 104, 61, 182, 114 (101) Combinations of sequence numbers 155, 137, 142, 188, 127, 85, 5, 1, 16, 196, 84, 53, 187, 38, 67, 110, 4, 176, 24, 177, 101, 193, 175, 100, 109, 145, 48, 88, 54, 71, 152, 89, 133, 39, 91, 159, 149, 104, 182, 93, 114 (102) Combinations of sequence numbers 87, 188, 127, 1, 80, 183, 45, 187, 189, 110, 128, 4, 200, 102, 26, 177, 101, 193, 175, 145, 178, 88, 96, 174, 117, 92, 152, 111, 133, 39, 91, 159, 149, 82, 171, 51, 55, 150, 182, 93, 114, 12 (103) Combinations of sequence numbers 121, 155, 188, 127, 85, 146, 196, 53, 187, 189, 110, 32, 56, 26, 101, 193, 175, 100, 109, 199, 97, 145, 178, 48, 63, 10, 88, 59, 54, 108, 152, 111, 133, 39, 7, 197, 159, 149, 82, 182, 114 (104) Combinations of sequence numbers 121, 155, 87, 188, 127, 85, 1, 80, 84, 198, 187, 189, 194, 110, 200, 102, 86, 193, 175, 118, 75, 97, 145, 125, 178, 88, 59, 37, 92, 134, 152, 111, 39, 159, 149, 82, 20, 51, 150, 182, 114 (105) Combinations of sequence numbers 137, 95, 87, 142, 188, 127, 85, 1, 79, 196, 187, 189, 67, 110, 136, 41, 4, 24, 19, 177, 101, 193, 118, 100, 105, 97, 48, 54, 191, 174, 108, 152, 111, 133, 39, 159, 149, 171, 18, 182, 114 (106) Combinations of sequence numbers 95, 87, 188, 127, 146, 5, 196, 161, 84, 187, 14, 189, 154, 194, 110, 128, 176, 24, 68, 200, 185, 193, 175, 43, 109, 97, 145, 178, 48, 54, 174, 92, 152, 113, 39, 159, 149, 82, 55, 114, 23 (107) Combinations of sequence numbers 121, 155, 137, 87, 188, 127, 85, 79, 129, 16, 84, 14, 189, 67, 110, 124, 136, 41, 176, 24, 68, 185, 193, 175, 109, 97, 145, 178, 120, 73, 152, 111, 133, 113, 39, 91, 159, 149, 150, 182, 114 (108) Combinations of sequence numbers 155, 137, 168, 188, 127, 85, 1, 80, 79, 183, 196, 172, 84, 187, 189, 110, 41, 68, 185, 175, 75, 100, 109, 97, 145, 178, 48, 98, 88, 135, 54, 108, 92, 73, 111, 133, 39, 91, 149, 82, 150, 114 (109) Combinations of sequence numbers 13, 155, 132, 87, 168, 188, 127, 5, 1, 196, 84, 110, 6, 124, 41, 90, 176, 81, 24, 143, 68, 200, 101, 193, 175, 100, 109, 169, 178, 47, 174, 152, 111, 133, 39, 91, 149, 82, 61, 18, 182, 114 (110) Combinations of sequence numbers 121, 115, 155, 168, 142, 188, 127, 85, 1, 16, 196, 161, 187, 14, 189, 67, 110, 4, 176, 200, 193, 175, 25, 100, 167, 145, 178, 59, 54, 174, 108, 152, 111, 133, 113, 39, 91, 159, 82, 104, 182, 114, 23 (111) Combinations of sequence numbers 179, 115, 142, 188, 127, 146, 79, 196, 161, 187, 189, 194, 110, 4, 68, 177, 101, 193, 175, 100, 109, 145, 48, 59, 174, 108, 99, 152, 133, 113, 39, 149, 70, 82, 104, 140, 61, 103, 77, 55, 182, 114, 50 (112) Combinations of sequence numbers 13, 121, 155, 132, 95, 87, 168, 188, 127, 1, 16, 196, 84, 198, 189, 38, 110, 124, 4, 176, 24, 200, 102, 148, 185, 193, 175, 25, 109, 145, 125, 178, 10, 59, 37, 108, 141, 111, 133, 39, 159, 149, 82, 150, 182, 114 (113) Combinations of sequence numbers 179, 121, 95, 188, 127, 85, 1, 79, 16, 84, 53, 198, 187, 38, 194, 110, 136, 78, 4, 176, 193, 175, 75, 100, 109, 97, 145, 48, 88, 59, 54, 37, 152, 111, 113, 39, 91, 159, 149, 82, 171, 46, 150, 182, 114 (114) Combinations of sequence numbers 179, 115, 155, 87, 168, 188, 127, 85, 1, 16, 196, 198, 14, 110, 176, 24, 143, 68, 200, 193, 175, 118, 109, 97, 125, 178, 88, 83, 59, 47, 54, 120, 108, 163, 111, 133, 39, 91, 159, 149, 82, 46, 55, 182, 114

[0543] Furthermore, as a non-limiting example of the combination of hippocampal atrophy markers (target nucleic acids) used in the present invention, the following examples illustrate combinations of a polynucleotide consisting of the base sequence represented by Sequence ID No. 1 and a polynucleotide of a hippocampal atrophy marker selected from Tables 3 to 6. The combination of hippocampal atrophy markers (target nucleic acids) may also be a combination of miRNA or human miRNA corresponding to the following combinations. (1) Combination of sequence numbers 127, 1, and 110 (2) Combinations of sequence numbers 1, 110, 3, and 114 (3) Combinations of sequence numbers 137, 1, 110, 111, and 114 (4) Combinations of sequence numbers 155, 127, 5, 1, 154, and 110 (5) Combinations of sequence numbers 155, 87, 1, 154, 110, 73, 133, 149, and 114 (6) Combinations of sequence numbers 30, 1, 110, 128, 145, 3, 159, and 114 (7) Combinations of sequence numbers 127, 5, 1, 154, 110, 3, 73, and 114 (8) Combinations of sequence numbers 155, 5, 1, 110, 100, 145, 54, 133, and 114 (9) Combinations of sequence numbers 188, 5, 1, 38, 110, 152, 133, 159, and 114 (10) Combinations of sequence numbers 155, 1, 110, 100, 145, 54, 152, 133, 159, and 114 (11) Combinations of sequence numbers 137, 188, 127, 5, 1, 110, 145, 3, 152, 180, and 114 (12) Combinations of sequence numbers 155, 188, 1, 110, 75, 3, 71, 152, 133, 159, 149, and 114 (13) Combinations of sequence numbers 179, 121, 137, 5, 1, 183, 110, 185, 3, 54, 152, and 114 (14) Combinations of sequence numbers 155, 188, 127, 30, 5, 1, 53, 110, 109, 145, 152, and 159 (15) Combinations of sequence numbers 155, 188, 127, 1, 196, 189, 110, 109, 71, 152, 133, 149, and 114 (16) Combinations of sequence numbers 155, 137, 127, 1, 110, 193, 175, 109, 3, 152, 133, 180, and 114 (17) Combinations of sequence numbers 155, 142, 1, 154, 110, 100, 109, 145, 152, 133, 39, 104, 114 (18) Combinations of sequence numbers 155, 137, 188, 127, 5, 1, 187, 189, 110, 26, 109, 71, 152, and 114 (19) Combinations of sequence numbers 155, 188, 127, 1, 189, 110, 78, 185, 100, 71, 152, 133, 149, and 114 (20) Combinations of sequence numbers 121, 155, 188, 1, 79, 198, 154, 110, 100, 109, 54, 133, 104, and 114 (21) Combinations of sequence numbers 155, 142, 188, 127, 1, 196, 189, 110, 175, 100, 109, 145, 3, 174, and 114 (22) Combinations of sequence numbers 121, 155, 188, 127, 1, 110, 4, 100, 109, 145, 71, 152, 133, 82, and 114 (23) Combinations of sequence numbers 155, 142, 188, 127, 1, 189, 110, 100, 109, 174, 71, 133, 57, 51, 114 (24) Combinations of sequence numbers 155, 188, 127, 1, 154, 110, 58, 100, 109, 54, 71, 73, 133, 149, and 114 (25) Combinations of sequence numbers 155, 142, 188, 127, 1, 189, 110, 100, 145, 174, 152, 133, 149, 51, and 114 (26) Combinations of sequence numbers 179, 155, 137, 188, 127, 1, 138, 110, 193, 100, 145, 10, 152, 51, and 114 (27) Combinations of sequence numbers 155, 142, 188, 30, 1, 53, 110, 109, 145, 54, 96, 174, 152, 2, 51, 114 (28) Combinations of sequence numbers 155, 188, 127, 30, 1, 189, 194, 110, 100, 109, 145, 3, 71, 152, 133, 82, 114 (29) Combinations of sequence numbers 155, 137, 188, 127, 85, 30, 1, 110, 175, 100, 145, 54, 71, 152, 159, and 114 (30) Combinations of sequence numbers 155, 188, 127, 1, 110, 78, 185, 175, 100, 145, 152, 133, 149, 82, and 51 (31) Combinations of sequence numbers 155, 188, 127, 1, 198, 110, 86, 175, 100, 109, 174, 152, 133, 159, 149, 93, and 114 (32) Combinations of sequence numbers 155, 188, 127, 1, 110, 175, 145, 3, 152, 133, 180, 39, 159, 149, 77, and 114 (33) Combinations of sequence numbers 155, 188, 127, 5, 1, 196, 53, 154, 110, 58, 54, 152, 133, 82, 114 (34) Combinations of sequence numbers 179, 188, 127, 1, 110, 102, 175, 75, 100, 109, 3, 54, 152, 190, 133, 159, 2 (35) Combinations of sequence numbers 155, 137, 188, 127, 1, 196, 189, 110, 109, 145, 3, 73, 152, 133, 2, 82, 114 (36) Combinations of sequence numbers 155, 188, 127, 1, 198, 110, 68, 175, 75, 100, 54, 71, 73, 133, 149, 77, and 114 (37) Combinations of sequence numbers 121, 155, 87, 188, 127, 30, 1, 161, 110, 193, 109, 145, 135, 71, 152, 82, 114 (38) Combinations of sequence numbers 155, 87, 188, 127, 1, 198, 154, 110, 100, 174, 73, 152, 133, 159, 82, 51, 114 (39) Combinations of sequence numbers 155, 137, 87, 188, 127, 1, 198, 110, 68, 101, 100, 109, 145, 54, 152, 149, 51, and 114 (40) Combinations of sequence numbers 121, 155, 188, 127, 1, 198, 110, 75, 109, 145, 54, 152, 133, 82, 104, and 114 (41) Combinations of sequence numbers 155, 137, 87, 142, 188, 127, 1, 110, 185, 175, 100, 145, 174, 152, 141, 133, and 180 (42) Combinations of sequence numbers 155, 142, 188, 127, 1, 189, 154, 110, 71, 73, 152, 159, 149, 82, 51, 182, 114 (43) Combinations of sequence numbers 155, 188, 127, 5, 1, 79, 154, 110, 75, 3, 54, 108, 71, 73, 152, 133, 114 (44) Combinations of sequence numbers 155, 142, 127, 1, 189, 154, 110, 109, 3, 174, 108, 71, 133, 91, 159, 82, 104, 114 (45) Combinations of sequence numbers 121, 137, 188, 127, 1, 196, 189, 110, 175, 109, 3, 54, 191, 152, 133, 149, 82, and 114 (46) Combinations of sequence numbers 142, 188, 127, 1, 198, 110, 175, 100, 109, 145, 133, 180, 91, 159, 149, 82, 182, 114 (47) Combinations of sequence numbers 121, 155, 137, 188, 127, 85, 5, 1, 110, 100, 109, 3, 54, 73, 152, 133, 159, 114 (48) Combinations of sequence numbers 155, 188, 127, 1, 138, 198, 110, 68, 100, 109, 48, 3, 71, 152, 141, 133, 91, 182 (49) Combinations of sequence numbers 155, 137, 142, 188, 127, 1, 110, 109, 174, 71, 152, 111, 133, 180, 159, 149, 51, 114 (50) Combinations of sequence numbers 155, 137, 188, 127, 30, 1, 161, 154, 194, 110, 178, 10, 152, 111, 133, 180, 114 (51) Combinations of sequence numbers 179, 155, 188, 127, 1, 161, 110, 175, 109, 62, 125, 10, 54, 71, 152, 133, 180, 114 (52) Combinations of sequence numbers 155, 188, 127, 1, 110, 193, 175, 145, 48, 10, 71, 152, 141, 133, 180, 182, 114 (53) Combinations of sequence numbers 155, 137, 87, 188, 127, 1, 189, 194, 110, 193, 100, 10, 111, 133, 180, 159, 149, and 114 (54) Combinations of sequence numbers 155, 188, 5, 1, 154, 110, 109, 3, 54, 71, 73, 163, 152, 133, 180, 82, 104, 114 (55) Combinations of sequence numbers 155, 137, 188, 127, 30, 1, 17, 110, 193, 145, 71, 152, 111, 133, 180, 77, 150, and 114 (56) Combinations of sequence numbers 155, 137, 87, 142, 188, 127, 1, 198, 110, 58, 175, 109, 10, 152, 133, 149, 82, 93, and 114 (57) Combinations of sequence numbers 155, 188, 127, 5, 1, 196, 110, 68, 193, 109, 10, 54, 152, 133, 180, 82, and 114 (58) Combinations of sequence numbers 155, 142, 188, 127, 1, 110, 75, 109, 145, 10, 3, 71, 152, 133, 82, 51, and 114 (59) Combinations of sequence numbers 121, 155, 142, 188, 127, 1, 161, 154, 110, 175, 109, 71, 73, 152, 133, 149, 51, 114 (60) Combinations of sequence numbers 155, 137, 188, 127, 5, 1, 198, 154, 110, 193, 109, 3, 71, 152, 180, 159, 82, 104, and 114 (61) Combinations of sequence numbers 121, 155, 137, 142, 188, 127, 1, 154, 110, 175, 109, 108, 133, 159, 149, 82, 77, and 114 (62) Combinations of sequence numbers 155, 188, 127, 1, 189, 110, 26, 193, 175, 109, 145, 73, 152, 141, 133, 149, 82, 77, and 114 (63) Combinations of sequence numbers 155, 188, 127, 1, 162, 198, 189, 154, 110, 75, 100, 109, 54, 71, 152, 133, 82, 104, and 114 (64) Combinations of sequence numbers 121, 155, 137, 188, 127, 1, 110, 185, 69, 100, 109, 3, 174, 71, 133, 180, 159, 82, and 114 (65) Combinations of sequence numbers 179, 155, 188, 127, 1, 154, 110, 86, 193, 175, 75, 109, 145, 71, 133, 159, 82, and 114 (66) Combinations of sequence numbers 155, 87, 188, 127, 1, 84, 110, 193, 175, 100, 109, 71, 152, 133, 149, 82, 104, 77, 114 (67) Combinations of sequence numbers 155, 137, 188, 127, 1, 110, 175, 100, 145, 10, 135, 3, 71, 152, 133, 180, 149, 77, and 114 (68) Combinations of sequence numbers 155, 142, 188, 127, 1, 189, 154, 110, 175, 109, 145, 125, 174, 71, 152, 133, 91, 82, 114 (69) Combinations of sequence numbers 121, 142, 188, 127, 5, 1, 189, 154, 110, 100, 109, 145, 125, 174, 108, 71, 152, 82, 114 (70) Combinations of sequence numbers 155, 137, 87, 188, 127, 1, 198, 110, 185, 175, 100, 109, 145, 92, 152, 133, 180, 149, and 114 (71) Combinations of sequence numbers 155, 137, 87, 188, 127, 1, 161, 198, 110, 100, 109, 73, 152, 141, 133, 149, 182, and 114 (72) Combinations of sequence numbers 155, 142, 188, 1, 79, 198, 154, 110, 78, 185, 175, 100, 10, 152, 133, 180, 159, 51, and 114 (73) Combinations of sequence numbers 155, 137, 142, 188, 127, 1, 196, 189, 110, 78, 143, 200, 185, 145, 152, 133, 180, and 159 (74) Combinations of sequence numbers 155, 137, 188, 127, 1, 198, 110, 41, 101, 109, 145, 174, 73, 152, 159, 82, 51, 182, 114 (75) Combinations of sequence numbers 155, 142, 188, 127, 1, 80, 189, 110, 185, 153, 109, 145, 178, 174, 111, 133, 82, 104, and 114 (76) Combinations of sequence numbers 179, 155, 142, 188, 127, 1, 198, 194, 110, 68, 185, 101, 100, 109, 96, 152, 133, 180, and 149 (77) Combinations of sequence numbers 121, 155, 87, 188, 127, 5, 1, 198, 194, 110, 68, 193, 145, 152, 180, 159, 149, 182, and 114 (78) Combinations of sequence numbers 155, 137, 127, 1, 198, 110, 175, 100, 109, 54, 152, 133, 180, 39, 91, 149, 2, 82, 114 (79) Combinations of sequence numbers 121, 155, 137, 87, 142, 188, 127, 1, 198, 110, 56, 193, 109, 10, 3, 152, 180, 104, 182, 114 (80) Combinations of sequence numbers 121, 137, 87, 188, 127, 1, 187, 189, 110, 193, 109, 145, 135, 3, 152, 133, 159, 2, 82, 114 (81) Combinations of sequence numbers 155, 137, 188, 127, 1, 79, 198, 110, 86, 100, 109, 3, 174, 71, 152, 133, 91, 149, 82, 114 (82) Combinations of sequence numbers 155, 137, 188, 127, 1, 198, 110, 193, 100, 109, 145, 98, 3, 71, 152, 133, 159, 82, 150, 114 (83) Combinations of sequence numbers 155, 137, 188, 127, 1, 110, 153, 193, 75, 109, 88, 174, 71, 152, 133, 180, 149, 82, 51, 114 (84) Combinations of sequence numbers 155, 87, 188, 127, 1, 161, 198, 110, 175, 109, 169, 145, 178, 10, 92, 133, 159, 82, 104, and 114 (85) Combinations of sequence numbers 155, 87, 142, 188, 127, 1, 154, 194, 110, 101, 75, 100, 109, 145, 152, 133, 180, 82, and 114 (86) Combinations of sequence numbers 155, 137, 87, 127, 1, 110, 185, 175, 173, 109, 145, 133, 180, 91, 159, 149, 104, 77, 114 (87) Combinations of sequence numbers 155, 142, 188, 127, 1, 196, 110, 58, 185, 175, 75, 100, 109, 145, 125, 3, 91, 2, 82, 114 (88) Combinations of sequence numbers 121, 137, 142, 188, 127, 1, 154, 110, 175, 100, 109, 145, 88, 3, 54, 174, 152, 133, 82, 182, 114 (89) Combinations of sequence numbers 121, 137, 87, 188, 127, 1, 53, 110, 185, 175, 109, 152, 133, 91, 159, 149, 82, 104, 77, 150, 114 (90) Combinations of sequence numbers 155, 142, 188, 127, 30, 1, 196, 198, 189, 154, 110, 109, 145, 10, 174, 152, 133, 159, 82, 114 (91) Combinations of sequence numbers 179, 155, 188, 127, 1, 198, 110, 101, 175, 118, 109, 145, 3, 37, 73, 133, 91, 149, 82, 77, and 114 (92) Combinations of sequence numbers 155, 137, 87, 188, 127, 1, 196, 154, 110, 68, 26, 178, 71, 152, 133, 180, 91, 149, 82, 114 (93) Combinations of sequence numbers 121, 155, 137, 188, 127, 1, 79, 198, 110, 86, 75, 100, 109, 3, 152, 133, 149, 2, 82, 182, 114 (94) Combinations of sequence numbers 155, 137, 188, 127, 5, 1, 84, 198, 194, 110, 75, 100, 109, 145, 48, 71, 152, 133, 82, 114 (95) Combinations of sequence numbers 155, 142, 188, 127, 1, 79, 196, 154, 110, 41, 31, 109, 145, 48, 54, 174, 108, 71, 133, 82, and 114 (96) Combinations of sequence numbers 121, 155, 188, 127, 1, 161, 198, 189, 110, 78, 100, 178, 71, 152, 133, 159, 149, 104, 182, 114 (97) Combinations of sequence numbers 155, 188, 127, 1, 79, 189, 110, 176, 175, 109, 145, 48, 71, 73, 152, 133, 91, 159, 82, 77, 114 (98) Combinations of sequence numbers 155, 87, 142, 188, 127, 1, 196, 17, 189, 110, 153, 101, 175, 100, 109, 133, 180, 149, 51, and 114 (99) Combinations of sequence numbers 121, 155, 188, 127, 85, 1, 198, 189, 154, 110, 109, 145, 125, 178, 71, 152, 141, 133, 180, 159, 114 (100) Combinations of sequence numbers 155, 188, 127, 1, 198, 187, 110, 68, 175, 100, 109, 145, 125, 10, 3, 71, 152, 133, 82, 182, 114 (101) Combinations o...

Claims

1. miR-6757-5p, miR-3131, miR-4706, miR-5001-5p, miR-3180-3p, miR-642b-3p, miR-4655-5p, miR-6819-5p, miR-937-5p, miR-4688, miR-6741-5p, miR-7107-5p, miR-4271, miR-1229-5p, miR-4707-5p, miR-6808-5p, miR-4656, miR-6076, miR-6762-5p, miR-7109-5p, miR-6732-5p, miR-3195, miR-7150, miR-642a-3p, miR-1249-5p, miR-3185, miR-4689, miR-3141, miR-6840-3p, miR-3135b, miR-1914-3p, miR-4446-3p, miR-4433b-3p, miR-6877-5p, miR-6848-5p, miR-3620-5p, miR-6825-5p, miR-5739, miR-3663-3p, miR-4695-5p, miR-3162-5p, miR-3679-5p, miR-8059, miR-7110-5p, miR-1275, miR-6779-5p, miR-197-5p, miR-6845-5p, miR-4327, miR-4723-5p, miR-4530, miR-6771-5p, miR-614, miR-92a-2-5p, miR-6891-5p, miR-6124, miR-4687-3p, miR-4442, miR-7977, miR-6785-5p, miR-4497, miR-8071, miR-663b, miR-3180, miR-4251, miR-1285-3p, miR-6870-5p, miR-4484, miR-4476, miR-6749-5p, miR-4454, miR-6893-5p, miR-6085, miR-4787-5p, miR-149-3p, miR-7704, miR-6125, miR-6090, miR-3197, miR-6850-5p, miR-4467, miR-6885-5p, miR-6803-5p, miR-6798-5p, miR-6780b-5p, miR-6768-5p, miR-5100, miR-6724-5p, miR-6879-5p, miR-7108-5p, miR-4649-5p, which are hippocampal atrophy markersA kit for detecting hippocampal atrophy using blood, serum, or plasma as a sample, comprising a nucleic acid probe capable of specifically binding to at least one polynucleotide selected from the group consisting of miR-4739, miR-6089, miR-1908-5p, miR-4516, miR-2861, miR-4492, miR-4294, miR-6791-5p, miR-1469, miR-6752-5p, miR-4730, miR-6126, miR-6869-5p, miR-1268a, miR-6799-5p, miR-8069, miR-3621, and miR-4763-3p, and / or a primer capable of specifically recognizing and amplifying said polynucleotide.

2. The nucleic acid probe and / or primer is a polynucleotide of the following (a) to (e): (a) A polynucleotide consisting of a base sequence represented by any of sequence numbers 2, 1, 3 to 109, or a base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases. (b) A polynucleotide containing a base sequence represented by any of Sequence IDs 2, 1, 3 to 109, or a base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases. (c) A polynucleotide consisting of a nucleotide sequence represented by any of sequence numbers 2, 1, 3 to 109, or a nucleotide sequence complementary to the nucleotide sequence in which u is t, or a fragment thereof containing 15 or more consecutive nucleotides. (d) A polynucleotide containing a nucleotide sequence represented by any of sequence numbers 2, 1, 3 to 109, or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, or a fragment thereof containing 15 or more consecutive nucleotides, and (e) A polynucleotide that hybridizes with any of the polynucleotides in (a) or (c) under stringent conditions, the polynucleotide having a base sequence having at least 90% homology with a base sequence complementary to the base sequence of any of the polynucleotides in (a) or (c), The kit according to claim 1, wherein the polynucleotide is selected from the group consisting of the following.

3. The kit includes miR-1228-5p, miR-760, miR-187-5p, miR-7111-5p, miR-6088, miR-6805-3p, miR-4640-5p, miR-6721-5p, miR-6880-5p, miR-711, miR-128-1-5p, miR-4525, miR-486-3p, miR-6756-5p, miR-1260b, miR-3184-5p, miR-6075, miR-204-3p, miR-4728-5p, miR-4534, miR-4758-5p, miR-8063, miR-6836-3p, miR-6789-5p, miR-744-5p, miR-1909-3p, miR-887-3p, miR-4745-5p, miR-4433a-3p, miR-5090, miR-296-5p, miR-939-5p, miR-3648, miR-3196, miR-6722-3p, miR-6805-5p, miR-1202, miR-6775-5p, miR-6087, miR-6765-5p, miR-6875-5p, miR-4674, miR-1233-5p, miR-7114-5p, miR-5787, miR-8072, miR-3619-3p, miR-4632-5p, miR-6800-5p, miR-4634, miR-4486, miR-6727-5p, miR-4505, miR-4725-3p, miR-1538, miR-320b, miR-1915-5p, miR-328-5p, miR-6820-5p, miR-6726-5p, miR-3665, miR-638, miR-762, miR-4466, miR-3940-5p, miR-1237-5p, miR-575, miR-3656, miR-4488, miR-4281, miR-6781-5p, miR-4532, miR-4665-5p, miR-6816-5p, miR-4508, miR-6784-5p, miR-6786-5p, miR-4741, miR-1343-5p, miR-1227-5p, miR-4734, miR-3960, miR-128-2-5p, miR-6743-5p, miR-663a, miR-6729-5p, miR-1915-3p, miR-1268b, miR-4651, which are another hippocampal atrophy marker.The kit according to claim 1 or 2, further comprising a nucleic acid probe capable of specifically binding to at least one polynucleotide selected from the group consisting of miR-3178 and miR-4463, and / or a primer capable of specifically recognizing and amplifying the polynucleotide.

4. The nucleic acid probe and / or primer is a polynucleotide of the following (f) to (j): (f) A polynucleotide consisting of a base sequence represented by any of sequence numbers 110 to 200, or a base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases. (g) A polynucleotide containing a base sequence represented by any of sequence numbers 110 to 200, or a base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases. (h) A polynucleotide consisting of a nucleotide sequence represented by any of sequence numbers 110 to 200, or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, or a fragment thereof containing 15 or more consecutive nucleotides. (i) A polynucleotide containing a nucleotide sequence represented by any of sequence numbers 110 to 200, or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, or a fragment thereof containing 15 or more consecutive nucleotides, and (j) A polynucleotide that hybridizes with any of the polynucleotides of (f) or (h) under stringent conditions, wherein the polynucleotide consists of a base sequence having at least 90% homology with a base sequence complementary to the base sequence of any of the polynucleotides of (f) or (h), The kit according to claim 3, wherein the polynucleotide is selected from the group consisting of the following.

5. miR-6757-5p, miR-3131, miR-4706, miR-5001-5p, miR-3180-3p, miR-642b-3p, miR-4655-5p, miR-6819-5p, miR-937-5p, miR-4688, miR-6741-5p, miR-7107-5p, miR-4271, miR-1229-5p, miR-4707-5p, miR-6808-5p, miR-4656, miR-6076, miR-6762-5p, miR-7109-5p, miR-6732-5p, miR-3195, miR-7150, miR-642a-3p, miR-1249-5p, miR-3185, miR-4689, miR-3141, miR-6840-3p, miR-3135b, miR-1914-3p, miR-4446-3p, miR-4433b-3p, miR-6877-5p, miR-6848-5p, miR-3620-5p, miR-6825-5p, miR-5739, miR-3663-3p, miR-4695-5p, miR-3162-5p, miR-3679-5p, miR-8059, miR-7110-5p, miR-1275, miR-6779-5p, miR-197-5p, miR-6845-5p, miR-4327, miR-4723-5p, miR-4530, miR-6771-5p, miR-614, miR-92a-2-5p, miR-6891-5p, miR-6124, miR-4687-3p, miR-4442, miR-7977, miR-6785-5p, miR-4497, miR-8071, miR-663b, miR-3180, miR-4251, miR-1285-3p, miR-6870-5p, miR-4484, miR-4476, miR-6749-5p, miR-4454, miR-6893-5p, miR-6085, miR-4787-5p, miR-149-3p, miR-7704, miR-6125, miR-6090, miR-3197, miR-6850-5p, miR-4467, miR-6885-5p, miR-6803-5p, miR-6798-5p, miR-6780b-5p, miR-6768-5p, miR-5100, miR-6724-5p, miR-6879-5p, miR-7108-5p, miR-A device for detecting hippocampal atrophy using blood, serum, or plasma as a sample, comprising a nucleic acid probe capable of specifically binding to at least one polynucleotide selected from the group consisting of miR-4739, miR-6089, miR-1908-5p, miR-4516, miR-2861, miR-4492, miR-4294, miR-6791-5p, miR-1469, miR-6752-5p, miR-4730, miR-6126, miR-6869-5p, miR-1268a, miR-6799-5p, miR-8069, miR-3621, and miR-4763-3p, and / or a primer capable of specifically recognizing and amplifying said polynucleotide.

6. The nucleic acid probe and / or primer is a polynucleotide of the following (a) to (e): (a) A polynucleotide consisting of a base sequence represented by any of sequence numbers 2, 1, 3 to 109, or a base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases. (b) A polynucleotide containing a base sequence represented by any of Sequence IDs 2, 1, 3 to 109, or a base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases. (c) A polynucleotide consisting of a nucleotide sequence represented by any of sequence numbers 2, 1, 3 to 109, or a nucleotide sequence complementary to the nucleotide sequence in which u is t, or a fragment thereof containing 15 or more consecutive nucleotides. (d) A polynucleotide containing a nucleotide sequence represented by any of sequence numbers 2, 1, 3 to 109, or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, or a fragment thereof containing 15 or more consecutive nucleotides, and (e) A polynucleotide that hybridizes with any of the polynucleotides in (a) or (c) under stringent conditions, the polynucleotide having a base sequence having at least 90% homology with a base sequence complementary to the base sequence of any of the polynucleotides in (a) or (c), The device according to claim 5, wherein the polynucleotide is selected from the group consisting of the following.

7. The device is miR-1228-5p, miR-760, miR-187-5p, miR-7111-5p, miR-6088, miR-6805-3p, miR-4640-5p, miR-6721-5p, miR-6880-5p, miR-711, miR-128-1-5p, miR-4525, miR-486-3p, miR-6756-5p, miR-1260b, miR-3184-5p, miR-6075, miR-204-3p, miR-4728-5p, miR-4534, miR-4758-5p, miR-8063, miR-6836-3p, miR-6789-5p, miR-744-5p, miR-1909-3p, miR-887-3p, miR-4745-5p, miR-4433a-3p, miR-5090, miR-296-5p, miR-939-5p, miR-3648, miR-3196, miR-6722-3p, miR-6805-5p, miR-1202, miR-6775-5p, miR-6087, miR-6765-5p, miR-6875-5p, miR-4674, miR-1233-5p, miR-7114-5p, miR-5787, miR-8072, miR-3619-3p, miR-4632-5p, miR-6800-5p, miR-4634, miR-4486, miR-6727-5p, miR-4505, miR-4725-3p, miR-1538, miR-320b, miR-1915-5p, miR-328-5p, miR-6820-5p, miR-6726-5p, miR-3665, miR-638, miR-762, miR-4466, miR-3940-5p, miR-1237-5p, miR-575, miR-3656, miR-4488, miR-4281, miR-6781-5p, miR-4532, miR-4665-5p, miR-6816-5p, miR-4508, miR-6784-5p, miR-6786-5p, miR-4741, miR-1343-5p, miR-1227-5p, miR-4734, miR-3960, miR-128-2-5p, miR-6743-5p, miR-663a, miR-6729-5p, miR-1915-3p, miR-1268b, miR-4651, which are another hippocampal atrophy marker.The device according to claim 5 or 6, further comprising a nucleic acid probe capable of specifically binding to at least one polynucleotide selected from the group consisting of miR-3178 and miR-4463, and / or a primer capable of specifically recognizing and amplifying the polynucleotide.

8. The nucleic acid probe and / or primer is a polynucleotide of the following (f) to (j): (f) A polynucleotide consisting of a base sequence represented by any of sequence numbers 110 to 200, or a base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases. (g) A polynucleotide containing a base sequence represented by any of sequence numbers 110 to 200, or a base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases. (h) A polynucleotide consisting of a nucleotide sequence represented by any of sequence numbers 110 to 200, or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, or a fragment thereof containing 15 or more consecutive nucleotides. (i) A polynucleotide containing a nucleotide sequence represented by any of sequence numbers 110 to 200, or a nucleotide sequence complementary to the nucleotide sequence in said nucleotide sequence where u is t, or a fragment thereof containing 15 or more consecutive nucleotides, and (j) A polynucleotide that hybridizes with any of the polynucleotides of (f) or (h) under stringent conditions, wherein the polynucleotide consists of a base sequence having at least 90% homology with a base sequence complementary to the base sequence of any of the polynucleotides of (f) or (h), The device according to claim 7, wherein the polynucleotide is selected from the group consisting of the following.

9. The device according to any one of claims 5 to 8, wherein the device is a device for measurement by hybridization technology.

10. The device according to claim 9, wherein the hybridization technology is nucleic acid array technology.

11. In the specimens of the subjects, the hippocampal atrophy markers miR-6757-5p, miR-3131, miR-4706, miR-5001-5p, miR-3180-3p, miR-642b-3p, miR-4655-5p, miR-6819-5p, miR-937-5p, miR-4688, miR-6741-5p, miR-7107-5p, miR-4271, miR-1229-5p, miR-4707-5p, miR-6808-5p, miR-4656, miR-6076, miR-6762-5p, miR-7109-5p, miR-6732-5p, miR-3195, miR-7150, miR-642a-3p, miR-1249-5p, miR-3185, miR-4689, miR-3141, miR-6840-3p, miR-3135b, miR-1914-3p, miR-4446-3p, miR-4433b-3p, miR-6877-5p, miR-6848-5p, miR-3620-5p, miR-6825-5p, miR-5739, miR-3663-3p, miR-4695-5p, miR-3162-5p, miR-3679-5p, miR-8059, miR-7110-5p, miR-1275, miR-6779-5p, miR-197-5p, miR-6845-5p, miR-4327, miR-4723-5p, miR-4530, miR-6771-5p, miR-614, miR-92a-2-5p, miR-6891-5p, miR-6124, miR-4687-3p, miR-4442, miR-7977, miR-6785-5p, miR-4497, miR-8071, miR-663b, miR-3180, miR-4251, miR-1285-3p, miR-6870-5p, miR-4484, miR-4476, miR-6749-5p, miR-4454, miR-6893-5p, miR-6085, miR-4787-5p, miR-149-3p, miR-7704, miR-6125, miR-6090, miR-3197, miR-6850-5p, miR-4467, miR-6885-5p, miR-6803-5p, miR-6798-5p, miR-6780b-5p, miR-6768-5p, miR-5100, miR-6724-5p, miR-6879-5p, miR-7108-5pThe expression level of at least one polynucleotide selected from the group consisting of miR-4649-5p, miR-4739, miR-6089, miR-1908-5p, miR-4516, miR-2861, miR-4492, miR-4294, miR-6791-5p, miR-1469, miR-6752-5p, miR-4730, miR-6126, miR-6869-5p, miR-1268a, miR-6799-5p, miR-8069, miR-3621, and miR-4763-3p was measured. A method for detecting hippocampal atrophy, comprising substituting the measured expression level of the polynucleotide into a discriminant formula, prepared using the expression levels of the polynucleotide in a sample from a subject known to have hippocampal atrophy and the expression levels of the polynucleotide in a sample from a subject known not to have hippocampal atrophy as training samples, which is capable of distinguishing between hippocampal atrophy and non-atrophy, and thereby evaluating whether or not the subject's hippocampus is atrophied, wherein the sample is blood, serum, or plasma.

12. The method according to claim 11, comprising measuring the expression level of the polynucleotide using the kit described in any one of claims 1 to 4 or the device described in any one of claims 5 to 10.

13. Other hippocampal atrophy markers, miR-1228-5p, miR-760, miR-187-5p, miR-7111-5p, miR-6088, miR-6805-3p, miR-4640-5p, miR-6721-5p, miR-6880-5p, miR-711, miR-128-1-5p, miR-4525, miR-486-3p, miR-6756-5p, miR-1260b, miR-3184-5p, miR-6075, miR-204-3p, miR-4728-5p, miR-4534, miR-4758-5p, miR-8063, miR-6836-3p, miR-6789-5p, miR-744-5p, miR-1909-3p, miR-887-3p, miR-4745-5p, miR-4433a-3p, miR-5090, miR-296-5p, miR-939-5p, miR-3648, miR-3196, miR-6722-3p, miR-6805-5p, miR-1202, miR-6775-5p, miR-6087, miR-6765-5p, miR-6875-5p, miR-4674, miR-1233-5p, miR-7114-5p, miR-5787, miR-8072, miR-3619-3p, miR-4632-5p, miR-6800-5p, miR-4634, miR-4486, miR-6727-5p, miR-4505, miR-4725-3p, miR-1538, miR-320b, miR-1915-5p, miR-328-5p, miR-6820-5p, miR-6726-5p, miR-3665, miR-638, miR-762, miR-4466, miR-3940-5p, miR-1237-5p, miR-575, miR-3656, miR-4488, miR-4281, miR-6781-5p, miR-4532, miR-4665-5p, miR-6816-5p, miR-4508, miR-6784-5p, miR-6786-5p, miR-4741, miR-1343-5p, miR-1227-5p, miR-4734, miR-3960, miR-128-2-5p, miR-6743-5p, miR-663a, miR-6729-5p, miR-1915-3p, miR-1268b, miR-4651The method according to claim 11 or 12, comprising measuring the expression level of at least one polynucleotide selected from the group consisting of miR-3178 and miR-4463, and further using the measured expression level to evaluate whether or not the hippocampus of the subject is atrophied.

14. The method according to any one of claims 11 to 13, wherein the subject is a human.

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