Since plasma β-amyloid (1–42) levels are increased in young adults with Down syndrome and associate with accelerated ageing in these patients (Obeid et al. 2016), we hypothesized that an increase of soluble β-amyloid, produced by γ-secretase-mediated proteolytic cleavage of excess APP, might disrupt the morphogenesis of developing neurons (Freude et al. 2011) and precipitate regulatory changes to dictate α3 subunit availability. Here, APP is linked to Down syndrome.