FLG and Alzheimer disease: At the molecular level, AD skin lesions exhibit significant downregulation of structural proteins such as filaggrin and claudin-1 (Melnik, 2015; Callou et al., 2022), as well as tight junction-associated proteins, among which Zonula Occludens- (ZO-) 1 and occludin shown to be significantly reduced in AD skin lesions (Yuki et al., 2016), and ZO-3 expression diminished in keratinocyte-based AD models (Hu et al., 2023; Trujillo-Paez et al., 2024).