TREM2 attenuates macrophage activation52 and microglia expressing the R47H variant have been reported to have a reduced capacity to bind to phospholipids in an AD model, suggesting that TREM2 senses changes in the lipid microenvironment that result from Aβ accumulation and neuronal degeneration, which triggers signals that activate microglial capacity to limit Aβ accumulation.53 As such, similar mechanisms related to the triggered activation of microglia by mutant huntingtin protein could underlie the more severe cognitive decline in patients with the R47H variant. Here, TREM2 is linked to Alzheimer disease.