APP and Alzheimer disease: AD, the first age-related dementia to be recognized [295] is defined by its pathology of extracellular amyloid plaques, containing fibrils of the amyloid-β (Aβ) peptides cleaved from the single pass transmembrane amyloid precursor protein (APP), and intracellular neurofibrillary tangles, containing hyperphosphorylated tau which is a microtubule binding and stabilizing protein with additional functions [296].