APP and Alzheimer disease: Individuals with Down syndrome (DS) have an overabundance of amyloid-β (Aβ) peptide production due to trisomy of chromosome 21, which harbors the Aβ-precursor protein (APP) gene (Oyama et al., 1994), and they typically develop Alzheimer’s disease (AD) pathology by the fifth decade of life (Davidson et al., 2018).