Figure 3 summarizes the probable pathogenic mechanisms of TREM2 in AD. TREM2 mutations may be associated with reduced microglial phagocytosis and elevated degree of neuroinflammation, leading to reduced amyloid clearance and increased Tau pathology. In the presence of APOE E4 allele, effects of TREM2 mutations and may result in more severe disease phenotype. Here, APOE is linked to Alzheimer disease.