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Cited by 114Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

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 +4 more·2021·Experimental & Molecular Medicine
DOI 10.1038/s12276-021-00714-8PMC PMC8741783
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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.

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  • The diminishing B cells in AD is more pronounced in females.

    “our findings revealed that the diminishing B cells in AD is more pronounced in females”

    From Distinct sex-specific DNA methylation differences in Alzheimer’s disease (2022) · cites this paper as [69]

    The Results section (‘Differential gene expression profiles in B cells’; page unavailable) reports fewer B cells in AD patients than in controls. It does not report a female–male comparison, so the claim that the decrease is more pronounced in females is not supported by this source. The citing sentence describes that comparison as the citing authors’ own finding. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Investigations on proportions and phenotypes of circulating B cells in AD patients compared to age-matched healthy controls have concluded in a significant reduction of both absolute numbers and percentages of blood B cells in AD patients.

    “Investigations performed on the proportions and phenotypes of circulating B cells in AD patients compared to age-matched healthy controls have concluded in a significant reduction of both the absolute numbers and percentages of blood B cells in AD patients [84 -87].”

    From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [84]

    The Results (Differential gene expression profiles in B cells; page unavailable) report a significantly lower B-cell percentage in 43 AD patients than in 41 normal controls. The Discussion also reports earlier findings of lower absolute B-cell numbers and percentages. Our copy does not establish that the controls were age-matched, so that qualifier is unsupported. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The number of peripheral B cells was negatively correlated to the severity of AD in one study.

    “The number of peripheral B cells was negatively correlated to the severity of AD in one study [84]”

    From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [84]

  • Several B cell differentially expressed genes are enriched in AD-related signaling pathways such as oxidative phosphorylation and neurodegenerative diseases.

    “Several of the B cell differentially expressed genes are enriched in AD-related signaling pathways such as oxidative phosphorylation and neurodegenerative diseases [84].”

    From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [84]

  • Single cell RNA sequencing of PBMCs of AD patients revealed altered gene expression in B cells.

    “Single cell RNA sequencing of PBMCs of AD patients revealed altered gene expression in B cells [84,94].”

    From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [84]

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Authors
Xiong, L.-L., Xue, L.-L., Du, R.-L., Niu, R.-Z., Chen, L., Chen, J., Hu, Q., Tan, Y.-X., Shang, H.-F., Liu, J., Yu, C.-Y., & Wang, T.-H.
Affiliations
  • Kunming University of Science and Technology (CN)
  • Sichuan University (CN)
  • Kunming Medical University (CN)
  • Southwest Medical University (CN)
Corresponding author
  • Liu, Jia
  • Wang, Ting-Hua
ORCID
Venue
Experimental & Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2021-12
Volume
53
Issue
12
Pages
1888-1901
ISSN
  • 1226-3613 (ISSN-L)
  • 2092-6413
DOI
10.1038/s12276-021-00714-8
PMC
PMC8741783
OpenAlex
W4200477198
Cited by
114
References
6
Citations by year
2026: 20 · 2025: 33 · 2024: 32 · 2023: 16 · 2022: 11 · 2021: 1 · 2012: 1
FWCI
9.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Experimental & Molecular Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (82160223, 2020YFS0043, 201903)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, B cells, peripheral blood mononuclear cells, biomarkers, disease progression, Clinical Dementia Rating, amyloid-beta, cognitive impairment, B-cell depletion, gene expression signatures
MeSH terms
Alzheimer Disease, Animals, B-Lymphocytes, Humans, Leukocytes, Mononuclear, Biomarkers, Amyloid beta-Peptides, Computational Biology, Gene Expression Profiling, Mice, Single-Cell Analysis, High-Throughput Nucleotide Sequencing

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