Loss of Y chromosome in Alzheimer's patients co-occurs with somatic mutations beyond CHIP drivers.

ABSTRACT: Loss of Y chromosome (LOY) and clonal hematopoiesis of indeterminate potential (CHIP) are common age-related events with implications for aging and Alzheimer disease (AD). LOY is linked to increased AD risk, whereas CHIP may be protective, and their co-occurrence remains unclear. We conducted whole-exome sequencing of CD4⁺ T cells, NK cells, and myeloid cells from AD patients and controls exhibiting LOY or retention of Y chromosome. We identified 39 variants in known myeloid and lymphoid driver genes, with up to 35% co-occurring with LOY in the same clone. In addition, we detected 192 unknown drivers of clonal hematopoiesis, enriched in AD-LOY individuals (odds ratio 4.8, P = 0.041). In myeloid cells, total driver burden correlated with LOY (ρ = 0.52, P = 0.00041).

SUBMITTER: Rychlicka-Buniowska E 

PROVIDER: S-EPMC12696397 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature