By using healthy, non-lesional and lesional AD skin with different Cldn-1 levels as well as RHE with different Cldn-1 levels induced by siRNA-mediated KD, we show here that there is a dose-dependent correlation in human epidermis between Cldn-1 levels and both, TJ barrier and overall epidermal barrier function. The gene discussed is CLDN1; the disease is Alzheimer disease.