PSEN2 and early-onset autosomal dominant Alzheimer disease: We now know that early onset AD (EOAD) is often inherited and linked to mutations in the three genes APP, PSEN1, and PSEN2, encoding β-amyloid precursor protein, presenilin 1, and presenilin 2, respectively (familial EOAD: EOFAD), whereas late onset AD (LOAD) is currently sporadic and modulated by increased numbers of genetic factors with low penetrance (genetic modulators or variants) particularly APOEε4, and environmental factors (Bertram and Tanzi, 2011; Duyckaerts and Dickson, 2011; Serrano-Pozo et al., 2011; Lowe and Kalaria, 2015).