138 results about "Amyloid" patented technology

The invention belongs to the technical field of analytical chemistry and the field of early screening of Alzheimer's disease, and particularly relates to an array sensor based on zirconium-based MOF nano-enzyme and application of the array sensor to detection of amyloid protein. The zirconium-based MOF nano-enzyme for detecting amyloid protein comprises UiO-66 (at) Pt, UiO-66 (at) Pd and UiO-66 (at) PtPd, and the array sensor based on the zirconium-based MOF nano-enzyme is constructed by sensing units which are respectively added with the UiO-66 (at) Pt, the UiO-66 (at) Pd and the UiO-66 (at) PtPd. According to the amyloid protein detection method based on the zirconium-based MOF nano-enzyme, rapid and sensitive detection of amyloid protein can be realized, the cost is low, the repeatability is good, and a new idea is provided for detection of amyloid protein related diseases.

The application discloses a kind of cognitive promotion method and system based on multi-modal data.The cognitive promotion method includes: obtaining the first multi-modal data before treatment of patient;Amyloid load grouping is carried out to patient based on the amyloid load in the brain of patient, to obtain the initial cognitive training scheme corresponding;Cognitive training is carried out based on initial cognitive training scheme during the treatment of patient, and the second multi-modal data during treatment is collected;Based on multi-modal data before and after treatment of patient, in combination with brain network group atlas, obtain the multi-modal change data of patient;The multi-modal change data of patient is input into preset model, to output the cognitive promotion scheme that cognitive index of patient is most improved, to push to patient and carry out cognitive training.The method will be integrated by A beta-PET data, functional nuclear magnetic resonance imaging data and event-related potential data, real-time evaluation of the neuroplasticity change of patient, to dynamically generate personalized cognitive promotion scheme.

This invention discloses a method and system for following up on magnetic resonance imaging (MRI) images of amyloid-related radiological abnormalities, belonging to the field of medical image processing. The method includes: acquiring multimodal MRI image data; performing bias field correction and intensity normalization based on a bias field fitting model to generate a first image set; performing global alignment and edge detection on the first image set to extract anatomical physical boundaries, generating brain region mask data; performing branch deformation field registration on the first image set within the brain parenchyma defined by the brain region mask data to generate a spatially aligned second image set; calculating the average intensity of normal brain parenchyma regions in the second image set to obtain a scaling factor, acquiring a three-dimensional residual image; performing anisotropic diffusion filtering denoising on the three-dimensional residual image, and performing differential denoising and morphological screening processing, outputting the detection results. This invention eliminates systematic artifacts caused by insufficient bias field correction.

To provide antibodies and antigen binding fragments thereof that are useful for diagnosis, prognosis and treatment of Alzheimer's disease or other β-amyloid-related diseases, and methods of making and using the antibodies or antigen binding fragments thereof.SOLUTION: The present invention provides an isolated monoclonal antibody or antigen-binding fragment thereof, comprising a heavy chain complementarity determining region 1 (HCDR1), HCDR2, HCDR3, a light chain complementarity determining region 1 (LCDR1), LCDR2, and LCDR3, having specific polypeptide sequences, wherein the antibody or antigen-binding fragment thereof specifically binds 3pE Ab, preferably human 3pE Ab.SELECTED DRAWING: None

The invention discloses an application of a pyruvate dehydrogenase kinase (PDKS) inhibitor in preparation of a composition for treating Alzheimer's disease (AD), and particularly discloses an application of the PDKs inhibitor in preparation of the composition for treating the AD. According to the invention, the level of oxidative phosphorylation (OXPHOS) of microglial cells is obviously enhanced, the inflammatory response of the microglial cells is effectively reduced, the migration and aggregation capabilities of the microglial cells are obviously improved, the capability of the microglial cells to phagocytize and degrade extracellular beta-amyloid protein (A beta) plaque is obviously enhanced, the cognitive function defect of AD model mice is effectively improved, and the application of the microglial cells in the treatment of the AD model mice is promoted. The preparation is simple, and the application is wide.

The invention discloses a non-degreasing biological tissue dyeing method and device. The dyeing method of the non-degreasing biological tissue comprises the following steps: a sample fixing step: fixing a biological tissue sample by adopting paraformaldehyde and / or glutaraldehyde; and a dyeing step: carrying out electrophoresis dyeing on the fixed biological tissue sample which is not degreased by using a nucleic acid dye and a beta-amyloid protein small molecule dye. According to the non-degreasing biological tissue dyeing method disclosed by the invention, the non-degreasing biological tissue is directly dyed, so that the damage of degreasing operation to a sample is avoided; moreover, the nucleic acid dye is combined with the beta-amyloid protein small molecule dye, so that the whole brain sample can be quickly and efficiently dyed, and high-resolution fluorescence labeling and three-dimensional space distribution imaging of beta-amyloid protein plaques in the whole brain range can be realized; the method is of great significance in revealing the spatial distribution pattern of beta-amyloid protein and explaining the pathogenesis of Alzheimer's disease.

The present invention relates to polymorphs of a nitrogen-containing heterocyclic compound. The polymorphs of the present invention can effectively enhance or reactivate synaptic plasticity, and inhibit or eliminate the accumulation of beta-amyloid, without causing side effects, thereby exerting a therapeutic effect on various nervous system diseases or neurodegenerative diseases. In addition, the polymorphs of the present invention exhibit excellent physicochemical properties, such as stability, solubility, hygroscopicity, and mechanical strength, and show excellent permeability to the blood-brain barrier (BBB).

The present invention relates to a water-soluble compound for the detection of beta-amyloid, and a production method thereof. The compound according to the present invention has excellent water-soluble properties, and thus can provide a water-soluble formulation for the detection of beta-amyloid. Accordingly, there is an effect that the compound can be useful as a composition for the detection of beta-amyloid through retinal imaging.

The invention discloses ICA1L derived peptide and application thereof in relieving Alzheimer disease A beta pathology. The amino acid sequence of the ICA1L derived peptide is shown as SEQ ID NO.01. The invention further discloses a preparation method of the ICA1L derived peptide. The compound can be combined with low-density lipoprotein receptor associated protein 1 (LRP1), inhibit K48 connection type ubiquitination of the LRP1 and prevent degradation through a proteasome pathway, so that the protein level of the LRP1 is stabilized, and the expression of beta-site APP lyase 1 is reduced to reduce the generation and deposition of beta-amyloid protein. In vitro, the peptide shows good biocompatibility and cell uptake ability; in vivo, the peptide has blood-brain barrier permeability, can be positioned in neurons, can significantly reduce hippocampus and cortex A beta plaque deposition in a 5xFAD mouse model through caudal vein injection, reduces BACE1 and beta-CTF levels, and improves the cognitive function. The invention further discloses an ICA1L-LRP1 regulatory axis, and a new strategy is provided for treatment of the Alzheimer's disease.

The application discloses a photosensitizer targeting beta amyloid, and a preparation method and application thereof. The photosensitizer is a photosensitizer with A-D-A configuration, and a structural formula thereof is shown as formula I. The photosensitizer synthesized in the application has a longer emission wavelength, and after being combined with beta amyloid, the fluorescence signal is obviously enhanced, and can effectively generate singlet oxygen, that is, the photosensitizer can target mark A beta protein, and is used for fluorescence imaging of the A beta protein; and after the photosensitizer synthesized in the application is combined with beta amyloid in the brain of an Alzheimer's disease (AD) model mouse, the cognitive ability of the AD mouse can be effectively improved, A beta-mediated neurotoxicity can be reduced, and clearance of A beta plaques can be promoted, that is, the photosensitizer can be used for early diagnosis and treatment of Alzheimer's disease.

The composition for predicting Alzheimer's disease prognosis comprising a detection reagent that specifically binds to any one or more genes selected from the group consisting of Nos1 (Nitric oxide synthase 1), Aph1B (Anterior pharynx defective 1 homolog B), Ryr3 (Ryanodine receptor 3), Atf6 (Activating transcriptional factor 6), Ip3r (Inositol trisphosphate receptor), Nep (Neprilysin), Cdk5 (cyclin dependent kinase 5) and Abad (Amyloid beta-binding alcohol dehydrogenase), a kit, and a method for providing information on Alzheimer's disease prognosis of the present invention can rapidly and accurately predict the prognosis of Alzheimer's disease, and can determine the prognosis for a drug by comparing the expression level before and after drug administration, so that an appropriate treatment direction can be determined according to the predicted prognosis. Therefore, they have an effect that can greatly contribute to the reduction of mortality due to Alzheimer's disease.

The present invention relates to an improved antibody specifically binding to amyloid-β oligomers (AβOs). Specifically, the present invention relates to an improved form of the antibody W20. Compared with the antibody W20, the improved form of the antibody W20 has a significantly improved affinity to AβOs, and can more significantly inhibit the aggregation of Aβ and the AβOs-induced toxicity of nerve cells, more effectively improve the cognition and memory functions of an Alzheimer's disease model mouse, and reduce pathological changes in the brain of the mouse. The improved form of the antibody can specifically bind to oligomers of an amyloid-β, α-synuclein, mHTT and SOD 1, can inhibit the aggregation and cytotoxicity of various amyloids, and has a better potential for treating various amyloid diseases, such as Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, than the antibody W20. The improved form of the antibody can specifically bind to a highly toxic amyloid protein oligomer Aβo*3F, and has a better AD diagnosis value. The amino acid sequence of the antibody W20 is as shown in SEQ ID NO: 1.

A pyrimidine-2,4-diamine compound and a preparation method and application thereof are provided. The pyrimidine-2,4-diamine compound of the present disclosure can be used in the research of biological or pharmacological phenomena and cathepsin C-involved signal pathway transduction and the evaluation of novel cathepsin C inhibitors. The pyrimidine-2,4-diamine compound is subjected to the screening of anti-cathepsin C activity in vitro and in vivo and proved to have strong inhibitory activity on cathepsin C. The pyrimidine-2,4-diamine compound is subjected to the screening of anti-NSP activity in vivo and proved to have strong inhibitory activity on NSP. The pyrimidine-2,4-diamine compound is subjected to the screening of anti-inflammatory activity in vivo and proved to have an effective therapeutic effect on inflammatory disease models. Meanwhile, the pyrimidine-2,4-diamine compound shows low toxicity and exhibits good application prospect.

The invention discloses a myocardial amyloidosis quantitative analysis method based on SPECT imaging and related equipment, and relates to the field of wisdom medical device.The method comprises the steps that firstly, three-dimensional SPECT original data of N time phases of a target patient in the cardiac cycle are collected, a mu graph is generated based on low-dose CT for registration and attenuation correction, and a dynamic image is reconstructed; and then an MR structure sequence under synchronous electrocardio gating is obtained, and SPECT and MR space standardization and partial volume effect correction processing are completed. And unifying the cardiac cycle image form through affine and nonlinear transformation, and generating a high-quality enhanced SPECT image. Finally, radioactive counting information is extracted on the basis of three-dimensional segmentation, multiple myocardial quantitative indexes are calculated, comprehensive analysis of myocardial functions is achieved in combination with left ventricular functional parameters, and accurate image support is provided for non-invasive diagnosis and curative effect evaluation of myocardial amyloidosis.

The present invention relates to a composite material comprising at least one textile universal polymer and protein fibres containing at least one amyloid structure. The invention also relates to a method for preparing such a material and to the use of such a material for adsorbing contaminants or extracting metal ions.

This invention discloses a sulfated arabinoglycoside, its preparation method, and its applications, belonging to the field of biomedical technology. The technical solution includes a sulfated arabinoglycoside derived from *Streptococcus linearis* polysaccharide; a degree of polymerization of 2-5; arabinose as the main monosaccharide, and containing galactose; the molar percentage of arabinose is not less than 80%, and the molar percentage of galactose is not more than 20%; the main chain is composed of (1→4)-β-L-pyranose arabinose groups, with the sulfate groups of the arabinose mainly substituted at the C-3 position. This invention is applied to inhibiting the abnormal aggregation of human pancreatic islet amyloid peptide (hIAPP), solving the problem of the lack of safe and effective intervention methods for the abnormal aggregation of human pancreatic islet amyloid peptide in existing technologies. It features stable raw material sources, high safety, a simple and mild preparation method suitable for large-scale preparation, and the ability to inhibit the abnormal aggregation of human pancreatic islet amyloid peptide and reduce pancreatic β-cell damage.

The application belongs to the technical field of biological medicine and molecular biology, and particularly relates to application of umbilical cord blood plasma-derived extracellular vesicles and related bioactive molecules thereof in treatment of Alzheimer's disease. Specifically, the application isolates extracellular vesicles (UCBP-sEVs) from umbilical cord blood plasma, which has the effect of improving Alzheimer's disease. Further research finds that high enrichment of miR-16-2-3p therein is a key molecule for mediating treatment of Alzheimer's disease. miR-16-2-3p targets and inhibits expression of ROCK2, reduces phosphorylation level of TFEB and promotes nuclear translocation of the same, activates microglial autophagy-lysosome pathway, and thus promotes phagocytosis and degradation of intracerebral beta amyloid, and therefore has good practical application value.

The present disclosure relates in some aspects to methods and compositions for detecting amyloid-related diseases in an individual.

Disclosed herein are methods for diagnosing, selecting, monitoring, and treating subjects having or suspected of having Alzheimer's disease (AD) or another disorder associated with amyloid accumulation in the brain using tau PET levels.

The present invention relates to a composition comprising HAPLN1 as an active ingredient for preventing or treating senile degenerative brain diseases. Specifically, recombinant human HAPLN1 protein (rhHAPLN1) lowers the protein level of p16 in cultured human astrocytes to inhibit cellular senescence caused by the accumulation of beta amyloid peptides, and further inhibits phosphorylation (p-p38 MAPK) of p38 MAPK protein, thereby also having the possibility of inhibiting inflammatory responses associated with the onset of Alzheimer's disease and Parkinson's disease. In addition, the recombinant human HAPLN1 protein (rhHAPLN1) exhibits significant memory and learning improvement effects in in vivo experiments performed using a mouse acute Alzheimer's disease model, and thus can be expected to exhibit preventive and therapeutic effects against Alzheimer's disease that may occur with aging and the like. In addition, the inhibitory effect of the rhHAPLN1 protein on cellular senescence and inflammatory responses of astrocytes can provide a very important clue for establishing prevention and treatment strategies not only for aging itself but also for brain functions, motor behaviors, memory, seizures, dementia, brain tumors, and the like.

The present disclosure relates to identifying an individual as having or at risk of developing amyloid-positive dementia based on marker molecules amyloid beta 40 (A beta 40), amyloid beta 42 (A beta 42), and total Tau (tTau), the use of said marker molecule for identifying an individual having or at risk of developing amyloid-positive dementia, and a method for detecting an individual having an increased combination value of said marker molecule.

The application discloses a fusion protein CHC targeting soluble IL-17RD, a preparation method and application thereof. The fusion protein CHC is formed by connecting and fusing two sIL-17RD neutralizing nanobodies CQ5 and CQ13 with human serum albumin (HSA) through a linker, and the structure is CQ5-Linker-CHC-Linker-CQ13, and the amino acid sequence is shown as SEQ ID NO. 1. The application further provides a gene sequence coding the fusion protein and an adeno-associated virus AAV-PHP.eB carrier containing the gene. The neutralizing nanobody fusion protein can specifically bind and neutralize the biological function of sIL-17RD, regulate the brain vascular endothelial cell homeostasis by directly inhibiting the inflammatory response of brain vascular endothelial cells induced by TNF-alpha and indirectly inhibiting the activation of microglial cells. The application can be used for treating or preventing neurodegenerative diseases such as Alzheimer's disease, and has the effects of protecting vascular injury, improving learning and memory and cognitive impairment, reducing beta-amyloid plaque deposition, reducing neuron loss and glial cell activation and the like.

Antibodies that bind human beta-amyloid, peptide, methods of detecting, measuring and treating amyloidogenic disorders with said antibodies, pharmaceutical compositions comprising the antibodies and methods of manufacture are provided.

The present invention relates to a nasal fluid sample obtained from a subject, the nasal fluid sample comprising one or more marker protein amyloid beta (A beta), phosphorylated Tau (pTau) and / or total Tau (tTau). The invention further relates to a nasal fluid sample comprising one or more marker proteins A [beta], pTau and / or tTau for use in a method for aiding in the diagnosis of a degenerative disease of the nervous system, and to the use of a nasal fluid sample comprising one or more marker proteins A [beta], pTau and / or tTau for aiding in the diagnosis of a degenerative disease of the nervous system. The invention further relates to a method for aiding the diagnosis of a nervous system degenerative disease in a subject / individual.

Provided herein is the use of a compound of Formula I:or a pharmaceutically acceptable salt thereof, for treating a disease characterized by amyloid and amyloid-like aggregates, e.g., Alzheimer's disease.

Methods and compositions for manipulating metabolism in astrocytes to improve astrocytic and neuronal function, as well as individual pathology hallmarks and symptoms during the development of neurodegeneration by increasing PPARα expression and activity specifically in astrocytes within the central nervous system to treat a variety of neurodegenerative conditions including but not limited to conditions involving neuronal lipid dysregulation, oxidative damage, accumulation of β-amyloid or other protein aggregates, dementia, and motor dysfunction. Also provided are methods of treating peripheral metabolic dysfunction associated with neurodegenerative conditions.

Disclosed herein are methods of diagnosing, selecting, monitoring, and treating subjects with Alzheimer's disease (AD) or suspected of having AD or another disorder associated with amyloid accumulation in the brain.

The present application discloses a protein marker for early pregnancy detection of mammals, and particularly relates to a hidden marker protein serum amyloid A of early pregnancy test paper. Protein sequencing used in the present application adopts liquid chromatography-mass spectrometry (LC-MS) technology, sample correlation is compared through Venn, sample correlation, PCA and PLS-DA analysis; protein function annotation is carried out through GO, KEGG, COG and Pfam, and subcellular localization prediction is carried out; difference protein, protein set and difference metabolite are calculated and counted; correlation analysis of proteome and transcriptome is carried out, difference protein of sheep serum in early pregnancy is obtained, and a key marker protein of early pregnancy of sheep is screened, which provides a basis for unknown early pregnancy detection of sheep.

The present disclosure relates to a polypeptide analog or a derivative thereof, and a preparation method and use thereof, and particularly to an agonistic polypeptide analog or a derivative thereof of an insulin amyloid polypeptide receptor. The polypeptide analog or the derivative thereof provided by the present disclosure has good agonistic activity on the insulin amyloid polypeptide receptor, has the characteristics of good stability, high activity, etc. at the same time, and can be used for treating and preventing diseases related to the insulin amyloid polypeptide receptor, such as body weight abnormality, especially obesity and overweight.

The present application provides anti-Aβ constructs (e.g., anti-Aβ antibodies) that bind to Aβ (e.g., Aβ40 and Aβ42), nucleic acid molecules encoding an amino acid sequence of the anti-Aβ constructs, vectors comprising the nucleic acid molecules, host cells containing the vectors, methods of preparing the anti-Aβ constructs, pharmaceutical compositions containing the anti-Aβ constructs, and methods of using the anti-Aβ constructs or compositions.