MAPT and Alzheimer disease: The endogenous mechanism of cell death of LC neurons, which triggers the pathogenic cascade of AD (see below), has been well established by many studies (Burke et al., 1999; Kang et al., 2020, 2022), and it has also been established that hyperphosphorylated tau protein expression and Aβ accumulation occur prior to other regions of the brain (Mather and Harley, 2016).