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Mosaic chromosomal alterations in blood are associated with an increased risk of Alzheimer's disease

Naito, T.; Hirata, K.; Jang, B.; Lakhani, C. M.; Buonfiglioli, A.; Lee, W.-P.; Valladares, O.; Wang, L.-S.; Okada, Y.; Won, H.-H.; Papapetrou, E. P.; Marro, S. G.; Knowles, D. A.; Raj, T.

2025-06-04 genetic and genomic medicine
10.1101/2025.05.29.25328544 medRxiv
Show abstract

Mosaic chromosomal alterations (mCAs) in blood, a form of clonal hematopoiesis, have been linked to various diseases, but their role in Alzheimers disease (AD) remains unclear. We analyzed blood whole-genome sequencing (WGS) data from 24,049 individuals in the Alzheimers Disease Sequencing Project and found that autosomal mCAs were significantly associated with increased AD risk (odds ratio = 1.27; P = 1.3 x 10-5). This association varied by ancestry, mCA subtype, APOE {varepsilon}4 allele status, and chromosomal location. Using matched blood WGS and brain single-nucleus RNA-seq data, we identified microglia-annotated cells in the brain carrying the same mCAs found in blood. These findings suggest that blood mCAs may contribute to AD pathogenesis, potentially through infiltration into the brain and influencing local immune response.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.