Indeed, interest in the cholinergic hypothesis of AD has attracted recent attention, as virtually all older adults over the age of 70 show progressive accumulation of misfolded extracellular amyloid and intracellular over-phosphorylated tau proteins, but progressive neurodegeneration that accounts for AD-related cognitive impairment occurs only in ~10% of this population (Kok et al., 2009; Deture and Dickson, 2019). Here, MAPT is linked to Alzheimer disease.