Premature development of AD pathology is common in DS, with most individuals displaying AD-related pathology, such as amyloid-β (Aβ) plaques, accumulation of hyper-phosphorylated tau (p-tau), markers of oxidative stress, neuroinflammation, and neurodegeneration by age 40 [257, 261, 263, 272–274]. The gene discussed is MAPT; the disease is Alzheimer disease.