MAPT and early-onset autosomal dominant Alzheimer disease: By 40 years of age, nearly all DS patients develop the hallmark neuropathologies of Alzheimer's disease (AD), including extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated tau (Head et al., 2012; Snyder et al., 2020).