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Single-cell RNA sequencing reveals B cells-related molecular biomarkers for Alzheimer's Disease

ABSTRACT: In the current study, differentially expressed cells subpopulations in PBMCs and differentially expressed genes in B cells were identified with 4 AD patients and 2 controls by single-cell sequencing analysis. Some correlations were found among the Clinical Dementia Rating (CDR) score of AD patients, the number variation of B cells and the expression changes of marker genes as the disease developed. The indispensable function of B cell in AD progression was further validated using AD mice. Our results obtained proof-of-concept identification of possible pathogenic cell types and molecular biomarkers underlying AD, concealing the feasibility of predicting disease biomarkers in certain special types of cells rather than in the overall blood and an AD diagnostic or early warning kit based on this single-cell RNA sequencing is urgently needed. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 at early stage, 2 at late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease of B cells in the blood of AD patients was detected and its reduction was closely correlated with the Clinical Dementia Rating (CDR) score of AD patients. Functional experiments were performed in AD mice to verify the role of B cell in AD progression, and the results demonstrated B cell depletion markedly aggravated the cognitive function and augmented the Aβ burden in AD mice. Importantly, 18 genes were found to be specifically up-regulated and 7 genes down-regulated in B cell as the disease proceeded, among which several exhibited close correlation with AD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE168522 | GEO | 2021/03/10

REPOSITORIES: GEO

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