For example, the interaction between ApoE and TREM2, another major risk factor for sporadic AD, has been reported to facilitate the uptake of Aβ by microglia, and AD-linked mutations in TREM2 impair the binding affinity of TREM2 for ApoE leading to Aβ accumulation in the brain (Yeh et al., 2016). Here, APOE is linked to Alzheimer disease.