DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease

Sci Rep. 2014 Nov 20;4:7130. doi: 10.1038/srep07130.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by senile plaques, neurofibrillary tangles, synaptic disruption, and neuronal loss. Several studies have demonstrated decreases of docosahexaenoic acid-containing phosphatidylcholines (DHA-PCs) in the AD brain. In this study, we used matrix-assisted laser desorption/ionization imaging mass spectrometry in postmortem AD brain to show that PC molecular species containing stearate and DHA, namely PC(18:0/22:6), was selectively depleted in the gray matter of patients with AD. Moreover, in the brain regions with marked amyloid β (Aβ) deposition, the magnitude of the PC(18:0/22:6) reduction significantly correlated with disease duration. Furthermore, at the molecular level, this depletion was associated with reduced levels of the postsynaptic protein PSD-95 but not the presynaptic protein synaptophysin. Interestingly, this reduction in PC(18:0/22:6) levels did not correlate with the degrees of Aβ deposition and neuronal loss in AD. The analysis of the correlations of key factors and disease duration showed that their effects on the disease time course were arranged in order as Aβ deposition, presynaptic disruption, postsynaptic disruption coupled with PC(18:0/22:6) reduction, and neuronal loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Autopsy
  • Brain Chemistry
  • Cell Death
  • Disease Progression
  • Disks Large Homolog 4 Protein
  • Docosahexaenoic Acids / chemistry*
  • Docosahexaenoic Acids / metabolism
  • Female
  • Gene Expression
  • Gray Matter / chemistry*
  • Gray Matter / metabolism
  • Gray Matter / pathology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neurons / metabolism
  • Neurons / pathology
  • Phosphatidylcholines / chemistry*
  • Phosphatidylcholines / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Synapses / chemistry
  • Synapses / metabolism
  • Synapses / pathology
  • Synaptophysin / genetics
  • Synaptophysin / metabolism*

Substances

  • Amyloid beta-Peptides
  • DLG4 protein, human
  • Disks Large Homolog 4 Protein
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Phosphatidylcholines
  • SYP protein, human
  • Synaptophysin
  • Docosahexaenoic Acids