APP and Alzheimer disease: Alzheimer dementia occurs more often in people with Down syndrome compared with the general population4,5 because the amyloid precursor protein gene is located on the triplicated chromosome 21.6 By age 40, nearly all people with Down syndrome exhibit neuritic plaques and neurofibrillary tangles, the neuropathological hallmarks of Alzheimer disease; however, a subset will not manifest clinical symptoms.5 Timing of diagnosis after onset can be variable as there are no established reference standard diagnostic assessments of Alzheimer dementia in people with Down syndrome.