While the early‐onset familial (autosomal dominant) AD accounts for < 5% of all cases and is associated with mutations in the AMYLOID PRECURSOR PROTEIN (APP), PRESENELIN1 (PSEN1), and PRESENELIN2 (PSEN2) genes,12 the majority (> 95%) of AD cases have late onset with no apparent familial linkage, presenting as sporadic AD (sAD, Figure 1)13, 14 whose etiology remains unclear. Here, PSEN2 is linked to Alzheimer disease.