MAPT and Alzheimer disease: Oxidative stress [35], lipid peroxidation, increased mtDNA modification or deletion, and disruption of Ca2+ homeostasis were repeatedly observed both in transgenic (tg) AD model mice and in the brains of AD patients [36,37,38] before the appearance of major AD neuropathological hallmarks, i.e., the deposition of the amyloid-β (Aβ) peptide into amyloid plaques and the phosphorylated tau protein in neurofibrillary tangles (NFTs) [39].