APP and Alzheimer disease: The amyloid precursor protein (APP) plays a major role in the pathophysiology of Alzheimer’s disease (AD), and because the APP gene resides on chromosome 21, its additional copy is primarily responsible for the fact that all people with DS develop AD brain pathology, including amyloid-β (Aβ) plaques and cerebral amyloid angiopathy, by age 40 (Epstein, 1990; Snyder et al., 2020).