MAPT and Alzheimer disease: DS in combination with AD dementia (DS + AD) occurs decades prior to sporadic AD, but recapitulates many of the pathological hallmarks, including amyloid-beta peptide (Aβ) containing senile plaques, tau-positive neurofibrillary tangles, cortical thinning, brain atrophy, and degeneration of basal forebrain cholinergic neurons (BFCNs) and the septohippocampal circuit [1,5,6,7,8,9].