Stereotypic persistent B cell receptor clonotypes in Alzheimer's Disease

We constructed B cell receptor (BCR) repertoires in silico using peripheral blood (PB) samples collected from 44 Alzheimer's Disease (AD) patients at baseline and 37 patients at follow-up. For the control group (CG), we used BCR repertoire data from the chronologically collected PB samples of 55 healthy volunteers vaccinated with SARS-CoV-2 mRNA. The AD patients shared 3,983 stereotypic non-naive BCR clonotypes not found in CG, and their degree of overlap between patient pairs were significantly higher than that of CG pairs, even with the SARS-CoV-2 spike protein triggering a concerted BCR response. Twenty stereotypic non-naive AD patient-specific BCR clonotypes co-existed in more than four patients and persisted throughout two sampling points. One of these BCR clonotypes encoded an antibody reactive to the Amyloid-beta 42 peptide. Our findings strongly suggest that AD patients are exposed to common (auto)antigens associated with disease pathology, and their BCR repertoires show unique signatures with diagnostic potential.