Mutation-resolved single-cell transcriptomics reveals enhanced β-amyloid clearance in TET2-mutant human monocytes.

Yang, Xiao; Fatima, Sameen; Sampere-Birlanga, Salvador; Ware, Akshay; Shumliakivska, Mariana; Zanders, Lukas; Radhakrishnan, Srisurekha; Luxán, Guillermo et al. · JCI Insight · 2026

basic_science · Level V

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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.

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