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[210423 Àú³Î¹ßÇ¥] Therapeutic B-cell depletion reverses progression of Alzheimer¡¯s disease

ÇÑÁöÈñ ¦¢ 2021-04-19

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Therapeutic B-cell depletion reverses progression of Alzheimer¡¯s disease

Abstract

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




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