Ceramides and sphingomyelinases in senile plaques

Neurobiol Dis. 2014 May:65:193-201. doi: 10.1016/j.nbd.2014.01.010. Epub 2014 Jan 28.

Abstract

The senile plaque is a hallmark lesion of Alzheimer disease (AD). We compared, without a priori, the lipidome of the senile plaques and of the adjacent plaque-free neuropil. The analysis by liquid chromatography coupled with electrospray ionization mass spectrometry revealed that laser microdissected senile plaques were enriched in saturated ceramides Cer(d18:1/18:0) and Cer(d18:1/20:0) by 33 and 78% respectively with respect to the surrounding neuropil. This accumulation of ceramides was not explained by their affinity for Aβ deposits: no interaction between ceramide-liposomes and Aβ fibrils was observed in vitro by surface plasmon resonance and fluorescent ceramide-liposomes showed no affinity for the senile plaques in AD brain tissue. Accumulation of ceramides could be, at least partially, the result of a local production by acid and neutral sphingomyelinases that we found to be present in the corona of the senile plaques.

Keywords: Alzheimer disease; Aβ peptide; Ceramides; Laser microdissection; Lipidomics; Lipids; Mass spectrometry; Senile plaques; Sphingomyelinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism
  • Apolipoproteins E / genetics
  • Ceramides / metabolism*
  • Chromatography, Liquid
  • Female
  • Humans
  • Male
  • Mass Spectrometry
  • Microdissection
  • Middle Aged
  • Plaque, Amyloid / etiology
  • Plaque, Amyloid / metabolism*
  • Sphingomyelin Phosphodiesterase / metabolism*
  • Surface Plasmon Resonance

Substances

  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Ceramides
  • Sphingomyelin Phosphodiesterase