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

Amyloid-β peptide (Aβ), derived from the amyloid-β 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 Aβ on neural progenitor cells (NPC). We found that the neurotoxic peptide Aβ25-35 induced apoptosis of both neurons and NPC in wild-type (wt) primary cortical cultures derived from mouse embryos. Contrary to neurons, NPC were also subjected to apoptosis in response to Aβ25-35 in both fas−/− and Z-VAD/fmk (the broad-spectrum caspase inhibitor)-treated wt cortical cultures indicating that Aβ triggers a Fas- and caspase-independent apoptotic pathway in NPC. Interestingly, we also show that Aβ induces neurospheres adherence and NPC neuronal differentiation. Further studies are thus needed in order to understand the role of Aβ effects on NPC in AD pathology. Understanding the mechanisms involved may also be essential for the development of new regenerative therapies in AD.