Postsynaptic density protein PSD-95 expression in Alzheimer's disease and okadaic acid induced neuritic retraction

Neurobiol Dis. 2008 Jun;30(3):408-419. doi: 10.1016/j.nbd.2008.02.012. Epub 2008 Mar 12.

Abstract

In order to understand how plasticity is related to neurodegeneration, we studied synaptic proteins with quantitative immunohistochemistry in the entorhinal cortex from Alzheimer patients and age-matched controls. We observed a significant decrease in presynaptic synaptophysin and an increase in postsynaptic density protein PSD-95, positively correlated with beta amyloid and phosphorylated Tau proteins in Alzheimer cases. Furthermore, Alzheimer-like neuritic retraction was generated in okadaic acid (OA) treated SH-SY5Y neuroblastoma cells with no decrease in PSD-95 expression. However, in a SH-SY5Y clone with decreased expression of transcription regulator LMO4 (as observed in Alzheimer's disease) and increased neuritic length, PSD-95 expression was enhanced but did not change with OA treatment. Therefore, increased PSD-95 immunoreactivity in the entorhinal cortex might result from compensatory mechanisms, as in the SH-SY5Y clone, whereas increased Alzheimer-like Tau phosphorylation is not related to PSD-95 expression, as suggested by the OA-treated cell models.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Disks Large Homolog 4 Protein
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Middle Aged
  • Neurites / drug effects
  • Neurites / pathology
  • Neurites / physiology*
  • Okadaic Acid / toxicity*
  • Phosphorylation
  • Up-Regulation / genetics
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • DLG4 protein, human
  • Disks Large Homolog 4 Protein
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • tau Proteins
  • Okadaic Acid