Neuronal models for Alzheimer's disease research frequently have limitations as a result of their nonhuman origin and/or transformed state. Here we examined the potential of readily accessible neural crest-derived human epidermal melanocytes isolated from elderly individuals as a model system for Alzheimer's disease research. The amyloidogenic isoforms of amyloid precursor protein (APP; isoforms APP751/770) and amyloid beta (Aβ)1–40 were detected in epidermal melanocytes using immunocytochemistry and western blotting. Incubation of epidermal melanocytes with aggregated Aβ1–40 peptide caused a concentration-dependent reduction in cell viability, whereas age-matched dermal fibroblasts remained unaffected. These findings suggest that epidermal melanocytes from elderly donors are capable of amyloidogenesis and are sensitive to Aβ1–40 cytotoxicity. Thus, these cells may provide a readily accessible human cell model for Alzheimer's disease research.