MAPT and Alzheimer disease: Prevailing evidence suggests that APOE protein has pleiotropic functions in the CNS, including being the major cholesterol and other lipid carriers.[63] In addition, APOE also plays critical role in neurotoxicity, tau phosphorylation, synaptic plasticity, neuroinflammation, vascular integrity, glucose metabolism, and mitochondrial function.[64] The differential influence of APOE isotypes on Aβ accumulation and clearance are critically involved in AD pathogenesis.