Fibrillar beta-amyloid impairs the late phase of long term potentiation

Curr Alzheimer Res. 2006 Jul;3(3):179-83. doi: 10.2174/156720506777632871.

Abstract

Synaptic dysfunction is involved in early stages of Alzheimer's disease (AD). Amyloid-beta peptides (Abeta), a neuropathologic hallmark of the disease, have been shown to alter synaptic function. Given that Abeta is present in different forms including monomeric, oligomeric and fibrillar species, we have investigated whether fibrillar Abeta impairs synaptic function. Here we report that a synthetic fibrillar form of Abeta impairs the late protein-synthesis dependent phase of LTP without affecting the early protein-synthesis independent phase. These findings add to previous reports that Abeta oligomers are highly toxic to cells and might cause synaptic dysfunction, and suggest that a therapeutic intervention in AD should include the use of drugs inhibiting and disassembling fibril formation in addition to drugs inhibiting oligomers formation.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / physiopathology
  • Amyloid / administration & dosage
  • Amyloid / chemical synthesis
  • Amyloid beta-Peptides / administration & dosage*
  • Amyloid beta-Peptides / chemical synthesis
  • Analysis of Variance
  • Animals
  • Electric Stimulation
  • Hippocampus / drug effects*
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Polymers / administration & dosage*
  • Polymers / chemical synthesis
  • Protein Structure, Secondary
  • Synaptic Transmission / drug effects*

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Polymers