PSEN1 and Alzheimer disease: Most cases of AD are sporadic and only a small percentage shows clear familial autosomal dominant inheritance: the familial cases are predominantly early-onset forms associated with fully penetrant mutations in the Amyloid precursor protein (APP), and the γ-secretases Presenilin 1 and 2 (PSEN1 and 2; Karch et al., 2014).