Human melanocytes as a model system for studies of Alzheimer disease

The aging process leads to increased vulnerability to injury and disease, resulting in a decline in 1 or more organ systems that is incompatible with life. One of the most devastating age-associated neurodegenerative disorders, Alzheimer disease, is characterized by neuronal loss and the extracellular deposition in the brain of beta-amyloid peptide, which is presumed to be causally related. Using cultured neural crest-derived cutaneous melanocytes, we find that in the presence of beta-amyloid, melanocytes, like neurons, undergo programmed cell death (apoptosis). Nerve growth factor, which has been reported to attenuate the loss of cholinergic neurons in Alzheimer disease, protects melanocytes from apoptosis induced by beta-amyloid. Moreover, beta-amyloid is a ligand for the 75-kD transmembrane neurotrophin receptor that belongs to the family of apoptotic receptors that generates a cell-death signal on activation. Our data suggest that neuronal death in Alzheimer disease is mediated by the interaction of beta-amyloid with the 75-kD neurotrophin receptor. Human melanocytes provide a valuable in vitro model for studies of Alzheimer disease and for development of potential therapies.