MAPT and Alzheimer disease: Tau misprocessing in ABCs involves (1) the interaction of tau with elements in the subcortical cytoskeleton and its phosphorylation of tau at characteristic AD-related sites, (2) the MT-mediated transport of hyperphosphorylated tau in association with vesicles and their accumulation in distal dendrites, and (3) the progressive MT loss and dendritic dysfunction in the immediate vicinity of these deposits, which may be exacerbated by localized secretion followed by extracellularly mediated toxicity.