In AD lesional skin, stainings often did not show the classical “tracer-stops” (Fig. 3a,a′,a′′), but Biotin-556 penetrated through occludin (Fig. 3b,b′,b′′), Cldn-1 (Fig. 3c,c′c′′) and Cldn-4 (Fig. 3d,d′,d′′) positive sites. The gene discussed is CLDN4; the disease is Alzheimer disease.