MAPT and Alzheimer disease: However, the exact cause of AD has not been fully elucidated, although many hypotheses on its etiology and pathogenesis have been put forward, including the Aβ cascade hypothesis [4], the misfolded tau protein hypothesis [5], the cholinergic hypothesis [6,7,8,9], oxidative stress [10], calcium dyshomeostasis [11,12], neuroinflammation [13,14] and the mitochondria cascade (or MAM) hypothesis [15,16].