UMMS Affiliation

Department of Psychiatry

Publication Date


Document Type



Immunology and Infectious Disease | Nervous System Diseases | Neurology | Neuroscience and Neurobiology | Psychiatry and Psychology | Translational Medical Research


The function of B cells in Alzheimer's disease (AD) is not fully understood. While immunoglobulins that target amyloid beta (Abeta) may interfere with plaque formation and hence progression of the disease, B cells may contribute beyond merely producing immunoglobulins. Here we show that AD is associated with accumulation of activated B cells in circulation, and with infiltration of B cells into the brain parenchyma, resulting in immunoglobulin deposits around Abeta plaques. Using three different murine transgenic models, we provide counterintuitive evidence that the AD progression requires B cells. Despite expression of the AD-fostering transgenes, the loss of B cells alone is sufficient to reduce Abeta plaque burden and disease-associated microglia. It reverses behavioral and memory deficits and restores TGFbeta(+) microglia, respectively. Moreover, therapeutic depletion of B cells at the onset of the disease retards AD progression in mice, suggesting that targeting B cells may also benefit AD patients.


B cells, Neuroimmunology, Translational immunology, Alzheimer's disease

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Copyright © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit

DOI of Published Version



Kim K, Wang X, Ragonnaud E, Bodogai M, Illouz T, DeLuca M, McDevitt RA, Gusev F, Okun E, Rogaev E, Biragyn A. Therapeutic B-cell depletion reverses progression of Alzheimer's disease. Nat Commun. 2021 Apr 12;12(1):2185. doi: 10.1038/s41467-021-22479-4. PMID: 33846335; PMCID: PMC8042032. Link to article on publisher's site

Journal/Book/Conference Title

Nature communications

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.