How TET2-mutant myeloid cells mitigate Alzheimer’s disease progression

Many age-related diseases are associated with clonal hematopoiesis (CH), but  how Alzheimer’s disease (AD) connected with CH is not well understood. 

The researchers in this study uncover a mutation-specific association between clonal hematopoiesis (CH) and Alzheimer’s disease (AD) in mice and humans.

TET2- mutant CH conferred lower (47%) odds of AD in humans and reduced AD (reduced cognitive decline and β-amyloid plaque formation) in a mouse model via enhanced peripheral immune cell infiltration, whereas DNMT3A-mutant CH had no impact on AD outcomes.

The authors also show that microglia-like cells were detected at an increased rate in Tet2-mutant marrow recipients, and TET2-mutant human induced pluripotent stem cell (iPSC)-derived microglia were more phagocytic and hyperinflammatory than DNMT3A-mutant or wild-type microglia. 

https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(25)00228-0

https://sciencemission.com/TET2-mutant-myeloid-cells-mitigate-Alzheimer%E2%80%99s-disease-progression