Effects of the monomeric, oligomeric, and fibrillar Abeta42 peptides on the proliferation and differentiation of adult neural stem cells from subventricular zone

J Neurochem. 2007 Jul;102(2):493-500. doi: 10.1111/j.1471-4159.2007.04499.x. Epub 2007 Apr 30.

Abstract

The incidence of amyloid plaques, composed mainly of beta-amyloid peptides (Abeta), does not correlate well with the severity of neurodegeneration in patients with Alzheimer's disease (AD). The effects of Abeta(42) on neurons or neural stem cells (NSCs) in terms of the aggregated form remain controversial. We prepared three forms of oligomeric, fibrillar, and monomeric Abeta(42) peptides and investigated their effects on the proliferation and neural differentiation of adult NSCs, according to the degree of aggregation or concentration. A low micromolar concentration (1 micromol/L) of oligomeric Abeta(42) increased the proliferation of adult NSCs remarkably in a neurosphere assay. It also enhanced the neuronal differentiation of adult NSCs and their ability to migrate. These results provide us with valuable information regarding the effects of Abeta(42) on NSCs in the brains of patients with AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / drug effects
  • Adult Stem Cells / metabolism*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Lateral Ventricles / cytology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Regeneration / physiology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Peptide Fragments / metabolism*
  • Peptide Fragments / toxicity
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Polymers / metabolism
  • Polymers / toxicity
  • Spheroids, Cellular
  • Telencephalon / cytology
  • Telencephalon / metabolism

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Polymers
  • amyloid beta-protein (1-42)