SPINK5 and Alzheimer disease: These include: (1) Specific HLA haplotypes (e.g., HLA-DR4, HLA-DQ8) that demonstrate established associations with both AD and multiple autoimmune disorders (46, 47); and (2) Variations in key epithelial barrier gene networks (e.g., FLG, SPINK5) that not only compromise skin barrier integrity but may also participate in systemic autoimmune responses through epigenetic regulation (48).