Prior activation state shapes the microglia response to antihuman TREM2 in a mouse model of Alzheimer's disease.

ABSTRACT: Triggering receptor expressed on myeloid cells 2 (TREM2) sustains microglia response to brain injury stimuli including apoptotic cells, myelin damage, and amyloid β (Aβ). Alzheimer's disease (AD) risk is associated with the TREM2^R47H variant, which impairs ligand binding and consequently microglia responses to Aβ pathology. Here, we show that TREM2 engagement by the mAb hT2AB as surrogate ligand activates microglia in 5XFAD transgenic mice that accumulate Aβ and express either the common TREM2 variant (TREM2^CV) or TREM2^R47H scRNA-seq of microglia from TREM2^CV-5XFAD mice treated once with control hIgG1 exposed four distinct trajectories of microglia activation leading to disease-associated (DAM), interferon-responsive (

SUBMITTER: Ellwanger DC 

PROVIDER: S-EPMC7826333 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature