A locked immunometabolic switch underlies TREM2 R47H loss of function in human iPSC-derived microglia.

ABSTRACT: Loss-of-function genetic variants of triggering receptor expressed on myeloid cells 2 (TREM2) are linked with an enhanced risk of developing dementias. Microglia, the resident immune cell of the brain, express TREM2, and microglial responses are implicated in dementia pathways. In a normal surveillance state, microglia use oxidative phosphorylation for their energy supply, but rely on the ability to undergo a metabolic switch to glycolysis to allow them to perform rapid plastic responses. We investigated the role of TREM2 on the microglial metabolic function in human patient iPSC-derived microglia expressing loss of function variants in TREM2. We show that these TREM2 variant iPSC-microglia, including the Alzheimer's disease R47H risk variant, exhibit significant metabolic deficits includi

SUBMITTER: Piers TM 

PROVIDER: S-EPMC7027848 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature