MAPT and Alzheimer disease: The amyloid cascade hypothesis proposed in 1992 by Hardy and Higgins suggests Aβ deposition in the brain initiates AD pathogenesis (Hardy and Higgins, 1992), with Aβ accumulating in cortical extracellular plaques approximately 10–30 years before dementia onset, contributing to subsequent the deposition of tau, synaptic loss, and cognitive decline (Long and Holtzman, 2019; Wang et al., 2022b).