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NeuroMolecular Medicine

, Volume 1, Issue 2, pp 125–135 | Cite as

Disruption of neurogenesis in the subventricular zone of adult mice, and in human cortical neuronal precursor cells in culture, by amyloid β-peptide

Implications for the pathogenesis of Alzheimer’s disease
  • Norman J. Haughey
  • Dong Liu
  • Avi Nath
  • Amy C. Borchard
  • Mark P. MattsonEmail author
Original Research

Abstract

The adult mammalian brain contains populations of stem cells that can proliferate and then differentiate into neurons or glia. The highest concentration of such neural progenitor cells (NPC) is located in the subventricular zone (SVZ) and these cells can produce new olfactory bulb and cerebral cortical neurons. NPC may provide a cellular reservoir for replacement of cells lost during normal cell turnover and after brain injury. However, neurogenesis does not compensate for neuronal loss in age-related neurodegenerative disorders such as Alzheimer’s disease (AD), suggesting the possibility that impaired neurogenesis contributes to the pathogenesis of such disorders. We now report that amyloid β-peptide (Aβ), a self-aggregating neurotoxic protein thought to cause AD, can impair neurogenesis in the SVZ/cerebral cortex of adult mice and in human cortical NPC in culture. The proliferation and migration of NPC in the SVZ of amyloid precursor protein (APP) mutant mice, and in mice receiving an intraventricular infusion of Aβ, were greatly decreased compared to control mice. Studies of NPC neurosphere cultures derived from human embryonic cerebral cortex showed that Aβ can suppress NPC proliferation and differentiation, and can induce apoptosis. The adverse effects of Aβ on neurogenesis were associated with a disruption of calcium regulation in the NPC. Our data show that Aβ can impair cortical neurogenesis, and suggest that this adverse effect of Aβ contributes to the depletion of neurons and the resulting olfactory and cognitive deficits in AD.

Index Entries

Apoptosis bromodeoxyuridine calcium learning and memory olfactory stem cells subventricular zone 

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Copyright information

© Humana Press Inc 2002

Authors and Affiliations

  • Norman J. Haughey
    • 1
  • Dong Liu
    • 1
  • Avi Nath
    • 2
  • Amy C. Borchard
    • 1
  • Mark P. Mattson
    • 1
    • 3
    Email author
  1. 1.Laboratory of NeurosciencesNational Institute on Aging Gerontology Research CenterBaltimore
  2. 2.Department of NeurologyUniversity of KentuckyLexington
  3. 3.Department of NeuroscienceJohns Hopkins University School of MedicineBaltimore

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