Amyloid-β peptide triggers Fas-independent apoptosis and differentiation of neural progenitor cells

Amyloid-beta peptide (A beta), derived from the amyloid-beta precursor protein (APP), plays a central role in the pathogenesis of Alzheimer's disease and induces neuronal apoptosis. Neural progenitor cells persist in the adult mammalian brain and continue to produce new neurons throughout the life. The aim of our study was to establish the effects of A on neural progenitor cells (NPC). We found that the neurotoxic peptide A beta 25-35 induced apoptosis of both neurons and NPC in wildtype (wt) primary cortical cultures derived from mouse embryos. Contrary to neurons, NPC were also subjected to apoptosis in response to A beta 25-35 in both fas(-/-) and Z-VAD/fmk (the broad-spectrum caspase inhibitor)-treated wt cortical cultures indicating that A beta triggers a Fas- and caspase-independent apoptotic pathway in NPC. Interestingly, we also show that A beta induces neurospheres adherence and NPC neuronal differentiation. Further studies are thus needed in order to understand the role of A effects on NPC in AD pathology. Understanding the mechanisms involved may also be essential for the development of new regenerative therapies in AD. (c) 2004 Elsevier Inc. All rights reserved.