Progenitor cells from the adult mouse brain acquire a neuronal phenotype in response to beta-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 beta-amyloid fragments (both beta AP(1-42) and beta AP(25-35)) on NPC proliferation, differentiation and survival. We show that neurospheres exposed to 25 mu M beta AP(25-35) or beta AP(1-42) for 24 It (a toxic condition for mature neurons) did not undergo apoptosis. Instead, beta AP(25-35) orientated nestin-negative precursors towards nestin-positive NPCs and turned nestin-positive NPCs into neuroblasts. Intracerebroventricular infusion of full-length beta AP(1-42) increased the population of PSA-NCAM-positive cells in the SVZ, without affecting proliferation. We conclude that beta AP influences the fate of progenitor cells, driving their differentiation towards a neuronal lineage.