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Stereotypic persistent B cell receptor clonotypes in Alzheimer’s Disease

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We constructed in silico B cell receptor (BCR) repertoires 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 the SARS-CoV2 mRNA vaccine. AD patients shared 3,983 stereotypic 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 SAS-CoV2 spike protein triggering a concerted BCR response. Many stereotypic AD patient-specific BCR clonotypes co-existed in more than four patients and persisted throughout the two sampling points. One of these BCR clonotypes encoded an antibody reactive to the A{beta}42 peptide. Our findings strongly suggest that AD patients are exposed to common (auto)antigens associated with disease pathology, and that their BCR repertoire signatures have high diagnostic potential.