A surprising pathogenic role of B cells in mice with Alzheimer’s disease

Abstract

Abstract The role of adaptive immune cells in Alzheimer’s disease (AD), a progressive neurodegenerative disease that associates with impaired clearance of toxic amyloid-b (Ab) peptide aggregates from the brain parenchyma, is rarely explored and mostly assumed to be beneficial. Here, using three, widely utilized transgenic AD mouse models (3xTgAD, APP/PS1, and 5xFAD mice), we provide counterintuitive evidence that the manifestation of AD requires B cells. Despite expression of the AD-fostering transgenes, the genetic loss of B cells or antibody-mediated depletion of circulating B cells at the onset of the disease is sufficient to reverse Aβ plaque burden and disease-associated microglia in the brains. The B-cell loss also ameliorates behavioral and memory deficits in AD mice. Mechanistically, AD we linked to infiltration of B cells into the brain parenchyma and production of immunoglobulins and pro-inflammatory factors. These results warrant a new look to B cells as important, pathogenic players of AD. As such, it underscores therapeutic value of B-cell inactivation in control AD progression 1. This work was supported by the Intramural Research Program, NIA/NIH.