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Single-cell RNA sequencing reveals B cell-related molecular biomarkers for Alzheimer's disease.
- Source :
-
Experimental & molecular medicine [Exp Mol Med] 2021 Dec; Vol. 53 (12), pp. 1888-1901. Date of Electronic Publication: 2021 Dec 08. - Publication Year :
- 2021
-
Abstract
- 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.<br /> (© 2021. The Author(s).)
- Subjects :
- Alzheimer Disease pathology
Amyloid beta-Peptides genetics
Amyloid beta-Peptides metabolism
Animals
B-Lymphocytes immunology
Computational Biology
High-Throughput Nucleotide Sequencing
Humans
Leukocytes, Mononuclear immunology
Leukocytes, Mononuclear metabolism
Mice
Single-Cell Analysis
Alzheimer Disease etiology
Alzheimer Disease metabolism
B-Lymphocytes metabolism
Biomarkers
Gene Expression Profiling
Subjects
Details
- Language :
- English
- ISSN :
- 2092-6413
- Volume :
- 53
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Experimental & molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 34880454
- Full Text :
- https://doi.org/10.1038/s12276-021-00714-8