Analysis of sequencing data from multiply affected extended pedigrees can be valuable for identifying extremely rare variants that are transmitted to affected individuals (Curtis, 2011) and this approach has been successful in identifying variants in the PLD3 (phospholipase D3) gene in late-onset Alzheimer's disease (Cruchaga et al., 2014). Here, PLD3 is linked to early-onset autosomal dominant Alzheimer disease.