The Alzheimer’s Prevention Initiative [8] is embarking on two clinical trials targeting cognitively unimpaired individuals at highest genetic risk for Alzheimer disease, one trial in an extended early-onset Columbian kindred carrying a fully penetrant presenilin 1 mutation, and the Generation Study (NCT02565511), a trial in individuals aged 60–75 y who carry two copies of the Alzheimer disease risk allele apolipoprotein E epsilon 4 (APOE-e4). The gene discussed is PSEN1; the disease is early-onset autosomal dominant Alzheimer disease.