Effects of different amyloid β-protein analogues on synaptic function

Cristian Ripoli, Roberto Piacentini, Elisa Riccardi, Lucia Leone, Domenica D. Li Puma, Gal Bitan, Claudio Grassi

Research output: Contribution to journalArticle

Abstract

Perisynaptic accumulations of amyloid β-protein (Aβ) play a critical role in the synaptic dysfunction underlying the cognitive impairment observed in Alzheimer's disease. The methionine residue at position 35 (Met35) in Aβ is highly subject to oxidation in Alzheimer's disease brains. In hippocampal brain slices we found that long-term potentiation at CA3-CA1 synapses was significantly inhibited by wild type Aβ42 in which Met35 is reduced, but not by Aβ42 harboring Met35 sulfoxide. Similar differences were observed when basal synaptic transmission was investigated in autaptic hippocampal neurons. The significant decreases in excitatory postsynaptic current amplitude, vesicle release probability and miniature excitatory postsynaptic current frequency caused by 20-minute exposure to wild type Aβ42 were not observed after exposure to Aβ42 harboring Met35 sulfoxide. With longer (24-hour) Aβ treatments, this early impairment of the presynaptic terminal function extended to involve the postsynaptic side as well. The Met35 oxidation also affected Aβ42 negative impact on dendritic spine density and expression of pre- and postsynaptic proteins (synaptophysin and postsynaptic density protein-95). Our findings suggest that oxidation of Met35 is critical for molecular, structural, and functional determinants of Aβ42 synaptotoxicity.

Original languageEnglish
Pages (from-to)1032-1044
Number of pages13
JournalNeurobiology of Aging
Volume34
Issue number4
DOIs
Publication statusPublished - Apr 2013

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Keywords

  • Alzheimer's disease
  • Amyloid-β protein
  • Dentritic spines
  • Long-term potentiation
  • MEPCS
  • Methionine 35
  • PSD-95
  • Synaptic transmission
  • Synaptophysin

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Ripoli, C., Piacentini, R., Riccardi, E., Leone, L., Li Puma, D. D., Bitan, G., & Grassi, C. (2013). Effects of different amyloid β-protein analogues on synaptic function. Neurobiology of Aging, 34(4), 1032-1044. https://doi.org/10.1016/j.neurobiolaging.2012.06.027