APOE and Alzheimer disease: There are several lines of evidence link cholesterol abnormalities to AD: 1) Cholesterol depletion in the neuronal PMs impairs neuronal activity (8, 9, 10); 2) Cholesterol affects the cleavage of amyloid precursor protein (APP) and the formation of amyloid plaques (11, 12, 13); 3) Cholesterol promotes tau aggregation (14, 15, 16); 4) ApoE4, a major risk factor for AD, is associated with dysregulation of cholesterol transport (17).