Most mouse models of AD to date involve either a systemic breakdown of the skin barrier (e.g. filaggrin/matted [Kawasaki et al., 2012; Saunders et al., 2013] or Adam17-deficient [Kobayashi et al., 2015]), or rely on heavy manipulations of the skin (e.g. tape stripping followed by antigen challenge (Oyoshi et al., 2012) or topical applications of inflammatory cytokines, such as IL-23 [Li et al., 2016]) and they may not reflect natural progression of AD. Here, ADAM17 is linked to Alzheimer disease.