MAPT and Alzheimer disease: The effects of APOE ε4 on AD risk have been proposed to include the following: inhibition of Aβ clearance and promotion of Aβ aggregation, tau pathology and tau-mediated neurodegeneration, impairment of microglia-inflammation response, disturbance of lipid transport, loss of synaptic integrity and plasticity, abnormal glucose metabolism, and disruption of cerebrovascular integrity and function [25].