Strikingly, individuals with DS have a 90% lifetime prevalence of Alzheimer's disease (AD),3 such that trisomy 21 is now seen as a genetic form of AD (DSAD) similar to autosomal dominant AD (ADAD), which is caused by mutations in the amyloid beta (Aβ) precursor protein (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2) genes. Here, PSEN2 is linked to Alzheimer disease.