Whereas rare variants of large effect in a few genes such as amyloid β protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) have been implicated in no more than 5% of all cases of Alzheimer’s disease, mostly early-onset alzheimer’s disease (Ballard et al., 2011), the aggregate effects of more common genetic variants with individually small effects are relevant for risk for more common, sporadic (nonfamilial) forms of the disease (Marioni et al., 2018). The gene discussed is PSEN1; the disease is early-onset autosomal dominant Alzheimer disease.