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Drugs for diagnosis and treatment of Alzheimer's disease

An Alzheimer's disease and drug technology, applied in the field of neuroscience, can solve the problems of difficult brain biopsy, limited sensitivity and specificity, and lack of early diagnosis methods for AD.

Inactive Publication Date: 2017-12-15
郁金泰 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, the lack of early diagnosis of AD is the biggest obstacle to the application of such therapies
At present, it is difficult to carry out brain biopsy in AD patients, and the sensitivity and specificity of AD diagnosis through medical history and scale evaluation are very limited

Method used

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  • Drugs for diagnosis and treatment of Alzheimer's disease
  • Drugs for diagnosis and treatment of Alzheimer's disease
  • Drugs for diagnosis and treatment of Alzheimer's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Embodiment 1 The experimental material and method that the present invention adopts

[0021] human subjects

[0022] This study complied with the Declaration of Helsinki and was approved by the Ethics Committee of Nanjing Medical University. The research objects come from healthy young people and old people among the active and retired employees of Nanjing First Hospital. All participants are Han Chinese and have no blood relationship with each other. Each participant signed a written consent form.

[0023] Purification and culture of monocytes from human circulating blood

[0024] According to the method described by Zondler and colleagues [6] , mononuclear cells were isolated from human venous whole blood. The general process is: use (Sigma-Aldrich Company) instrument, adopt density gradient centrifugation and CD-14 positive magnetic bead separation technology (Miltenyi Biotec Company) to realize cell separation. Resuspension of cells was performed in RPMI 1640...

Embodiment 2

[0053] Example 2 Trem1 can regulate the phagocytosis of mouse microglia on Aβ

[0054] As the only mononuclear phagocytes in the central nervous system (CNS), microglia participate in the clearance of Aβ through phagocytosis. To clarify the role of TREM1 in the phagocytosis of Aβ by microglia, we manipulated the expression of Trem1 in microglia isolated from WT pups using a lentiviral mechanism. After 72 hours of transduction, the expression level of Trem1 mRNA and the change of Trem1 protein level were measured by qRT-PCR and ELISA technology, respectively. Afterwards, the in vitro test method provided by Griciuc et al. was used to detect the effect of microglia on Aβ 1-42 phagocytosis and degradation. Knockout of Trem1 leads to internalization of Aβ in microglia of young WT mice 1-42 levels decreased by 52% (P1-42 The level increased nearly 1.7 times (P1-42 degradation index.

[0055] According to previous studies, APP / PSEN1 mice showed significant AD-related phenotypes ...

Embodiment 3

[0056] Example 3 During the progressive disease stage of APP / PSEN1 mice, the expression level of Trem1 on microglia is relatively stable.

[0057] Since TREM1 can promote microglia-mediated Aβ phagocytosis under AD conditions, we reasonably hypothesize that TREM1 may play a key role in AD progression. To test this hypothesis, we first explored the dynamic changes in the levels of Trem1 and its adapter protein Tyrobp in microglia in APP / PSEN1 mice at 1, 4, 7 and 10 months of age. During disease progression in APP / PSEN1 mice, the expression levels of Trem1 or Tyrobp did not change significantly (Trem1 mRNA level: P=0.31; Trem1 protein level: P=0.4; Tyrobp mRNA level: P=0.77). Meanwhile, we also did not find any significant differences in the expression levels of Trem1 or Tyrobp in microglia between APP / PSEN1 mice and their age-matched WT mice.

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Abstract

The invention discloses diagnosis and treatment methods of Alzheimer disease and a corresponding kit. Specifically, an expression level of TREM1 (Triggering Receptor Expressedon Myeloid 1) proteins directly influences a clearing-up capability of microglial cells on beta amyloid proteins, so that the beta amyloid proteins cannot be normally cleaned; and the TREM1 proteins can be used as diagnosis and treatment target spots of the Alzheimer disease.

Description

technical field [0001] The present invention belongs to the field of neuroscience. Specifically, the present invention relates to a diagnostic and therapeutic target for Alzheimer's disease (Alzheimer's disease, AD), as well as corresponding diagnostic and therapeutic methods and related kits. Background technique [0002] AD is the most common neurodegenerative disease clinically, with progressive memory, visuospatial and executive dysfunction as typical clinical manifestations [1] . In recent years, with the acceleration of aging, the number of AD patients in my country has increased significantly, which has brought a very heavy burden to patients, families and society. [2] . So far, the etiology of the disease is still unclear, and there is no effective treatment. [0003] According to existing studies, one of the main pathological features of AD is the accumulation of a large amount of β-amyloid protein (Amyloid-β, Aβ) in the brain, which induces a series of neurotox...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/68G01N33/68G01N33/53A61K48/00A61K45/00A61K39/395A61P25/28
CPCA61K39/3955A61K45/00A61K48/00C12Q1/6883C12Q2600/158G01N33/53G01N33/6896G01N2333/705G01N2800/2821
Inventor 郁金泰蒋腾张颖冬谭兰
Owner 郁金泰
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