APP and early-onset autosomal dominant Alzheimer disease: Amyloid precursor protein (APP) is a transmembrane protein implicated in the pathogenesis of Alzheimer's disease through its proteolytic processing, which generates amyloid-β (Aβ) peptides that aggregate into amyloid plaques.18,19 Among the various domains of APP, the E2 domain is particularly noteworthy due to its role in copper coordination.