TREM2 and Alzheimer disease: Very recently, Jain et al. reported an interesting finding that chronic activation of TREM2 receptor with a TREM2 antibody increased the activation of peri-plaque microglia, and surprisingly aggravated tau pathology and neurodegeneration in a mouse model of amyloidosis in which tau was injected directly into the brain to induce Aβ-dependent tau seeding/spreading.234 It is possible that the adverse effect of TREM2 at the later stage of AD is caused by the chronic activation of it (Fig. 5).