MAPT and Alzheimer disease: Cerebral hypoperfusion has been found to contribute to the pathological features of AD, including upregulation of beta-site amyloid precursor protein cleaving enzyme1 (BACE1) [87], aggregation of Aβ [88], and hyperphosphorylation of tau [89], which can lead to synaptic dysregulation, deficits of progressive spatial memory, and neuronal loss in AD [90].