MAPT and Alzheimer disease: The brain amyloid pathology is the major hallmark of AD, and the widely recognized model for AD progression suggests that Aβ pathogenesis may be an upstream event in AD and functions as a trigger of downstream pathways, including the tau-mediated toxicity, misfolding of hyperphosphorylated tau isoforms, tau accumulation in tangles, and proliferation of tau proteins leading to cortical neurodegeneration.