Therapeutic B-cell depletion reverses progression of Alzheimer’s disease

Ki Kim, Xin Wang, Emeline Ragonnaud, Monica Bodogai, Tomer Illouz, Marisa DeLuca, Ross A. McDevitt, Fedor Gusev, Eitan Okun, Evgeny Rogaev, Arya Biragyn

Research output: Contribution to journalArticlepeer-review

87 Scopus citations


The function of B cells in Alzheimer’s disease (AD) is not fully understood. While immunoglobulins that target amyloid beta (Aβ) 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 Aβ 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 Aβ plaque burden and disease-associated microglia. It reverses behavioral and memory deficits and restores TGFβ+ 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.

Original languageEnglish
Article number2185
JournalNature Communications
Issue number1
StatePublished - 12 Apr 2021

Bibliographical note

Publisher Copyright:
© 2021, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.


We are grateful to Dr. A. C. Chan (Genentech, Inc.) for providing anti-CD20 Ab; Drs. K. Becker, E. Lehrmann, and Y. Zhang (NIA) for microarray assay and bioinfor-matics analysis; and Mrs. A. Lustig (NIA) and Dr. Chandamany Arya (Lilly) for proofreading. This research was supported by the Intramural Research Program of the National Institute on Aging, NIH, and by grant NIH R01 AG054712-01A1.

FundersFunder number
National Institutes of Health
National Institute on AgingAG000778-04, ZIGAG000621
Center for Information TechnologyR01 AG054712-01A1


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