Antibody-regulated neurotoxic function of cell-surface ss-amyloid precursor protein

APP is a transmembrane precursor of beta -amyloid, and its mutations cause early-onset familial Alzheimer's disease. We report a toxic function of nor mal wild-type APP (wtABP). Treatment of neuronal F11 cells, immortalized em bryonic day 13 neurons, overexpressing wtAPP with anti-APP antibodies cause d death. Death was not induced by antibody in parental F11 cells. Death by antibody occurred through cell-surface APP, not through secreted APP, in a pertussis toxin-sensitive manner and was typical apoptosis, not observed in primary astrocytes or glioma cells overexpressing wtAPP, but observed in p rimary cortical neurons. Cell-surface APP thus performs a toxic function as an extracellularly controllable regulator of neuronal death. This study pr ovides a novel insight into the normal and pathological functions of cell-s urface wtAPP.