The effect of amyloid-β peptide on synaptic plasticity and memory is influenced by different isoforms, concentrations, and aggregation status

Neurobiol Aging. 2018 Nov;71:51-60. doi: 10.1016/j.neurobiolaging.2018.06.025. Epub 2018 Jul 18.

Abstract

The increase of oligomeric amyloid-beta (oAβ) has been related to synaptic dysfunction, thought to be the earliest event in Alzheimer's disease pathophysiology. Conversely, the suppression of endogenous Aβ impaired synaptic plasticity and memory, suggesting that the peptide is needed in the healthy brain. However, different species, aggregation forms and concentrations of Aβ might differently influence synaptic function/dysfunction. Here, we have tested the contribution of monomeric and oligomeric Aβ42 and Aβ40 at 200 nM and 200 pM concentrations on hippocampal long-term potentiation and spatial memory. We found that, when at 200 nM, oAβ40, oAβ42, and monomeric Aβ42 impaired long-term potentiation and memory, whereas only oAβ42 200 pM enhanced synaptic plasticity and memory and rescued the detrimental effect due to depletion of endogenous Aβ. Interestingly, quantification of monomer-like and oligomer-like species carried out by transmission electron microscopy revealed an increase of the monomer/oligomer ratio in the oAβ42 200 pM preparation, suggesting that the content of monomers and oligomers depends on the final concentration of the solution.

Keywords: Beta amyloid; Hippocampus; Long-term potentiation; Memory; Monomers; Oligomers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / administration & dosage
  • Amyloid beta-Peptides / physiology*
  • Animals
  • Female
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Humans
  • Long-Term Potentiation* / drug effects
  • Male
  • Mice, Inbred C57BL
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / physiology*
  • Protein Aggregates
  • Protein Isoforms / administration & dosage
  • Protein Isoforms / physiology
  • Spatial Memory / drug effects
  • Spatial Memory / physiology*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Protein Aggregates
  • Protein Isoforms
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)