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The Journal of Neuroscience, June 9, 2004, 24(23):5439-5444; doi:10.1523/JNEUROSCI.0974-04.2004

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Development/Plasticity/Repair
Neurogenic Effect of -Amyloid Peptide in the Development of Neural Stem Cells

Miguel A. López-Toledano and Michael L. Shelanski

Taub Institute for Research on Alzheimer's Disease and the Aging Brain and Department of Pathology, Columbia University, New York, New York 10032

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- peptide (A) on the survival and neuronal differentiation of cultured NSCs from striatum and hippocampus. We show that A 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 A peptide is not dependent on soluble factors released from the NSC progeny. Neurogenesis is induced by A42 and not A40 or A 25-35, and the activity appears to be a property of A oligomers and not fibrils.

These results suggest that A 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 disease.

Key words: Alzheimer; differentiation; hippocampus; stem cells; neurogenesis; amyloid peptide

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Received Nov 24, 2003; revised May 4, 2004; accepted May 5, 2004.

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