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KMID : 0620920210530121888
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Experimental & Molecular Medicine
2021 Volume.53 No. 12 p.1888 ~ p.1901
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Single-cell RNA sequencing reveals B cell?related molecular biomarkers for Alzheimer’s disease
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Xiong Liu-Lin
Xue Lu-Lu
Du Ruo-Lan
Niu Rui-Ze
Chen Li
Chen Jie
Hu Qiao
Tan Ya-Xin
Shang Hui-Fang
Liu Jia
Yu Chang-Yin
Wang Ting-Hua
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Abstract
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In recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer’s disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients’ Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aβ burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression.
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KEYWORD
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Cell death in the nervous system, Neurotrophic factors
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