Biomarker related to senescence glial cells and application of biomarker in diagnosis of Alzheimer's disease

A biomarker, glial cell technology, applied in disease diagnosis, biological testing, biomaterial analysis, etc., can solve problems such as detecting glial cells, and achieve the effect of improving the accuracy of diagnosis and the accuracy of differentiation

Pending Publication Date: 2021-12-21
UNIV OF SCI & TECH OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are currently no known reliable methods for detecting glial senescence in the living human brain

Method used

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  • Biomarker related to senescence glial cells and application of biomarker in diagnosis of Alzheimer's disease
  • Biomarker related to senescence glial cells and application of biomarker in diagnosis of Alzheimer's disease
  • Biomarker related to senescence glial cells and application of biomarker in diagnosis of Alzheimer's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Example 1 Types of Senescent Cells in AD Brain and Senescence-Related Molecules Expressed by Senescent Cells

[0055] 1. Collection of samples

[0056] All samples were collected from 195 patients aged 50 to 75 collected by the First Affiliated Hospital of University of Science and Technology of China, of which 58 were cognitively normal (CN), 37 were mild cognitive impairment (MCI), 78 cases of Alzheimer's disease (AD) and 22 cases of non-Alzheimer's dementia (non-AD), all patients received lumbar puncture, cerebrospinal fluid was divided into 200μl tubes and stored at -80 ℃. All CSF samples were processed in the same way, including numbering, concentration, aliquoting and storage under the same conditions. This study has been approved by the Ethics Committee of the First Affiliated Hospital of University of Science and Technology of China with the ethics number (2019KY-26). All participants gave informed consent.

[0057] 2. Experimental materials

[0058] 4% para...

Embodiment 2

[0064] Example 2 Expression of aging-related molecules in cerebrospinal fluid in different diagnostic groups (CN, MCI, AD, non-AD)

[0065] 1. Experimental materials

[0066] INNOTEST enzyme-linked immunosorbent assay (Fujirebio, 81585, 81583, 81581, 81579), ELISA kit (Sino Biological, SEK10307), multiplex Lu-minex platform (Luminex Corp, Luminex200), R&D LXSAHA kit

[0067] 2. Specific operation

[0068] (1) The levels of Aβ40, Aβ42, P-tau, and T-tau proteins in cerebrospinal fluid were detected by enzyme-linked immunosorbent assay, and the kit used was INNOTEST enzyme-linked immunosorbent assay (Fujirebio, 81585, 81583, 81581, 81579). Enzyme-linked immunosorbent assay is the use of antigen or antibody immobilization and antigen or antibody enzyme labeling. The antigen or antibody combined on the surface of the solid phase carrier still maintains its immunological activity, and the enzyme-labeled antigen or antibody retains both its immunological activity and enzyme activit...

Embodiment 3

[0076] Example 3 The relationship between the expression level of biomarkers in cerebrospinal fluid and AD pathological state and CDR score

[0077] 1. Specific operation

[0078] The states of Aβ and tau were defined by the ratio of Aβ42 / Aβ40 in CSF and the value of p-tau, respectively. Use the receiver operating characteristic (ROC) curve, SPSS 26.0 (SPSS.Inc, IBM) and the highest Youden index (highestYouden index) method to determine the cut-off value of Aβ and tau status, and the final result is that the ratio of Aβ42 / 40 is 0.0617 ( A+: Aβ42 / 400.0617), the P-tau value was 64.68 pg / ml (T+: P-tau>64.68; T-: P-tau<64.68). The two main pathological features in the AD brain are plaques formed by Aβ aggregation and tangles formed by excessive Tau fibrosis. Currently, the expression levels of Aβ42 / 40 and pTau in cerebrospinal fluid can best reflect these two pathological features. Therefore, these indicators are measured and analyzed in this embodiment, so that the pathology of...

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Abstract

The invention provides a biomarker which is used for monitoring the aging state of brain glial cells of a living body in real time and promoting early diagnosis of Alzheimer's disease, the biomarker comprises glial cell aging-related molecules, and the glial cell aging-related molecules are selected from YKL-40, HGF, MIF, S100B, TSP2, LCN2, SerpinA3 and any combination of the YKL-40, the HGF, the MIF, the S100B, the TSP2, the LCN2 and the SerpinA3. According to the present invention, the aging state of the glial cells in the brain of the living body can be easily monitored in real time, the diagnosis accuracy of the Alzheimer's disease and the normal cognitive individual can be easily improved, and the distinguishing accuracy of the Alzheimer's disease and the non-Alzheimer's disease can be improved.

Description

technical field [0001] The present invention relates to the fields of medicine and biology, in particular to a marker for distinguishing Alzheimer's disease from normal aging and non-Alzheimer's disease dementia based on senescent glial cell-related markers, as well as a detection method and application thereof. Background technique [0002] Alzheimer's disease (AD) is an age-related neurodegenerative disease, the main clinical manifestations are memory loss and neurodegeneration that aggravate with age, extensive amyloid (Aβ) deposition and Hyperphosphorylation of microtubule fibers (tau) is its two major pathological features. Cellular senescence is an important trigger for individuals to develop aging-related diseases, including neurodegenerative diseases. Cell senescence-related markers such as p16INK4a and CDK4 show abnormal accumulation in the brain of AD patients; in addition, the activity of senescence-associated β-galactosidase (SA-β-gal) is also significantly rai...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68
CPCG01N33/6896G01N33/6863G01N33/6872G01N33/74G01N2800/2821G01N2333/523G01N2333/47G01N2333/4753G01N2333/4704G01N2333/4727G01N2333/775G01N2333/8103
Inventor 申勇戴林斌高峰
Owner UNIV OF SCI & TECH OF CHINA
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