V6421 APP-inducible neuronal cells: A model system for investigating Alzheimer's disorders

APP is a precursor of beta amyloid deposited in Alzheimer's disease (AD). A lthough genetic studies established that mutations in APP cause familial AD (FAD), the mechanism for neuronal death by FAD mutants has not been well u nderstood. We established neuronal cells (F11/EcR/V642I cells) in which V64 2I APP was inducibly expressed by ecdysone. Treatment with ecdysone, but no t vehicle, killed most cells within a few days, with rounding, shrinkage, a nd detachment as well as nuclear fragmentation. Death was suppressed by Ac- DEVD-CHO and pertussis toxin. Electron microscopic analysis revealed that a poptosis occurred in ecdysone-treated cells. V642I-APP-induced death was su ppressed by the anti-AD factors estrogen and apoE2. These data demonstrate not only that expression of this FAD gene causes neuronal apoptosis, but th at F11/EcR/V642I cells, the first neuronal cells with inducible FAD gene ex pression, provide a useful model system in investigating AD disorders. (C) 2000 Academic Press.