Xiao Yang, Sameen Fatima, Salvador Sampere-Birlanga, Akshay Ware, Mariana Shumliakivska, Lukas Zanders, Srisurekha Radhakrishnan, Guillermo Luxán, David John, Stefan Günther, Silvia Mas-Peiro, Stefanie Dimmeler, Andreas M Zeiher, Wesley T Abplanalp
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.