Association of B cell profile and receptor repertoire with the progression of Alzheimer’s disease

Alzheimer’s disease (AD) is the most prevalent type of dementia. Reports have revealed that the peripheral immune system is linked to neuropathology; however, little is known about the contribution of B lymphocytes in AD. For this longitudinal study, 133 participants are included at baseline and second-year follow-up. Also, we analyze B cell receptor (BCR) repertoire data generated from a public dataset of three normal and 10 AD samples and perform BCR repertoire profiling and pairwise sharing analysis. As a result, longitudinal increase in B lymphocytes is associated with increased cerebral amyloid deposition and hyperactivates induced pluripotent stem cell-derived microglia with loss-of-function for beta-amyloid clearance. Patients with AD share similar class-switched BCR sequences with identical isotypes, despite the high somatic hypermutation rate. Thus, BCR repertoire profiling can lead to the development of individualized immune-based therapeutics and treatment. We provide evidence of both quantitative and qualitative changes in B lymphocytes during AD pathogenesis. [Display omitted] •Longitudinal increase in B cells is associated with cerebral amyloid deposition•B cell receptor repertoire profiling and pairwise sharing analysis are conducted•Patients with Alzheimer’s disease share similar class-switched BCR sequences•B cell-derived immunoglobulin G induces microglial dysfunction in the brain Park et al. perform longitudinal analyses, B cell receptor repertoire profiling, and imaging analyses to identify the contribution of B lymphocytes to Alzheimer’s disease pathology. They identify longitudinal increase in B lymphocyte populations, ensuing hyperactivation of microglia, and commonalities of BCR repertoires in Alzheimer’s disease.