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

2022; Cell Press; Volume: 40; Issue: 12 Linguagem: Inglês

10.1016/j.celrep.2022.111391

2639-1856

Jong‐Chan Park, Jinsung Noh, Sukjin Jang, Ki Hyun Kim, Hayoung Choi, Dongjoon Lee, Jieun Kim, Junho Chung, Dong Young Lee, Yonghee Lee, Hyunho Lee, Duck Kyun Yoo, Amos Chungwon Lee, Min Soo Byun, Dahyun Yi, Sun‐Ho Han, Sunghoon Kwon, Inhee Mook‐Jung,

Tryptophan and brain disorders

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.