The triplicate copy of chromosome 21 leads to the overproduction of amyloid precursor protein (APP; Wiseman et al. 2015), which is thought to contribute to early amyloid plaque accumulation (e.g., beginning in their teens and becoming nearly ubiquitous by 40 years of age; Mann 1988) that manifests with a striatum-dominant (i.e., striatum-first) pattern (Fig. 1; Handen et al. 2012; Lao et al. 2016; Annus et al. 2016). The gene discussed is APP; the disease is amyloidosis.