Downregulation of claudin-1, claudin-4, and claudin-23 was reported in non-lesional skin of patients with AD (48), while single nucleotide polymorphisms in the CLDN-1 gene encoding claudin-1 were found to be associated with AD in several cohort studies (49, 50), suggesting the involvement of tight junctions in the pathogenesis of AD. This evidence concerns the gene CLDN4 and Alzheimer disease.