Progenitor cells from the adult mouse brain acquire a neuronal phenotype in response to β-amyloid

Neurospheres from adult mouse subventricular zone (SVZ) were grown in suspension cultures for 12–15 days. Neurospheres consisted mainly of neural precursor cells (NPCs) immunoreactive for nestin and also contained nestin-negative precursors. We used these neurospheres to determine the effects of synthetic β-amyloid fragments (both βAP(1-42) and βAP(25-35)) on NPC proliferation, differentiation and survival. We show that neurospheres exposed to 25 μM βAP(25-35) or βAP(1-42) for 24 h (a toxic condition for mature neurons) did not undergo apoptosis. Instead, βAP(25-35) orientated nestin-negative precursors towards nestin-positive NPCs and turned nestin-positive NPCs into neuroblasts. Intracerebroventricular infusion of full-length βAP(1-42) increased the population of PSA-NCAM-positive cells in the SVZ, without affecting proliferation. We conclude that βAP influences the fate of progenitor cells, driving their differentiation towards a neuronal lineage.