JCI Insight. 2026 Aug 24;11(16):e208804. doi: 10.1172/jci.insight.208804. eCollection 2026 Aug 24.
ABSTRACT
TET2-driven clonal hematopoiesis has been associated with reduced Alzheimer's disease risk, but mechanisms in humans remain unclear. Using mutation-resolved single-cell transcriptomics, we distinguished TET2-mutant and wild-type monocytes within the same aged individuals and identified enrichment of phagocytosis and complement programs in mutant cells. TET2 silencing in human monocytes and macrophages recapitulated this phenotype and enhanced β-amyloid uptake, indicating mutation-specific bias of innate immunity toward aggregate clearance.
PMID:42635046 | DOI:10.1172/jci.insight.208804