HUMAN MELANOCYTES AS A MODEL SYSTEM FOR STUDIES OF ALZHEIMER-DISEASE

The aging process leads to increased vulnerability to injury and disea se, resulting in a decline in 1 or more organ systems that is incompat ible with life, One of the most devastating age-associated neurodegene rative 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 cres t-derived cutaneous melanocytes, we find that in the presence of beta- amyloid, melanocytes, like neurons, undergo programmed cell death (apo ptosis), Nerve growth factor, which has been reported to attenuate the loss of cholinergic neurons in Alzheimer disease, protects melanocyte s 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 signa l on activation, Our data suggest that neuronal death in Alzheimer dis ease is mediated by the interaction of beta-amyloid with the 75-kD neu rotrophin receptor, Human melanocytes provide a valuable in vitro mode l for studies of Alzheimer disease and for development of potential th erapies.