PSEN1 and inflammatory skin disease: Although various missense mutations in PSEN1 lead to autosomal-dominant AD (summarized in AlzForum Mutation Database), heterozygous loss-of-function mutations in PSEN1 as well as in Nicastrin and PEN2 (haploinsufficiency) have been shown to cause specific severe inflammatory skin disease, termed acne inversa in humans [15], reviewed in [16].