In the same Icelandic population where TREM2 p.Arg47His was identified as a risk factor for AD, Jonsson and colleagues also identified a rare variant in APP (rs63750847, p.Ala637Thr) with a MAF of 0.01%, that was significantly more common in elderly healthy individuals than in AD subjects, indicative of a protective effect against the development of AD. Here, APP is linked to Alzheimer disease.