Neurogenic Effect of β-Amyloid Peptide in the Development of Neural Stem Cells.

The adult mammalian brain contains neural stem cells (NSCs) with self-renewal and multilineage potential in the hippocampus and subventricular zone. However, neurogenesis from these areas does not compensate for neuronal loss in age-related neurodegenerative disorders such as Alzheimer's disease (AD). To test whether an impairment of neurogenesis could contribute to the pathogenesis of AD, we examined the effects of amyloid-β peptide (Aβ) on the survival and neuronal differentiation of cultured NSCs from striatum and hippocampus. We show that Aβ peptide does not impair the neurogenic rate in NSC progeny, but that it increases the total number of neurons in vitro in a dose-dependent manner. The neurogenic effect of Aβ peptide is not dependent on soluble factors released from the NSC progeny. Neurogenesis is induced by Aβ42 and not Aβ40 or Aβ 25-35, and the activity appears to be a property of Aβ oligomers and not fibrils. These results suggest that Aβ may have positive as well as deleterious actions, and that a knowledge of the mechanisms involved in the former could be valuable in exploiting the regenerative and plastic potential of the brain in preventing and treating Alzheimer's... [ABSTRACT FROM AUTHOR]