TREM2 Alzheimer's variant R47H causes similar transcriptional dysregulation to knockout, yet only subtle functional phenotypes in human iPSC-derived macrophages


The R47H mutation is not sufficient to cause gross phenotypic defects of human pMac under standard culture conditions. However, overlapping transcriptional defects with TREM2 KO supports the hypothesised partial loss-of-function effects of the R47H mutation. Furthermore, transcriptomics can guide us to more subtle phenotypic defects in the R47H cells, such as reduced cell adhesion, and can be used to predict targets for therapeutic intervention.

Authors Hall-Roberts H, Agarwal D, Obst J, Smith TB, Monzón-Sandoval J, Di Daniel E, Webber C, James WS, Mead E, Davis JB, Cowley SA
Journal Alzheimer's research & therapy
Publication Date 2020 Nov 16;12(1):151
PubMed 33198789
PubMed Central PMC7667762
DOI 10.1186/s13195-020-00709-z

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