Moderate decline in select synaptic markers in the prefrontal cortex (BA9) of patients with Alzheimer's disease at various cognitive stages

Sci Rep. 2018 Jan 17;8(1):938. doi: 10.1038/s41598-018-19154-y.


Synaptic loss, plaques and neurofibrillary tangles are viewed as hallmarks of Alzheimer's disease (AD). This study investigated synaptic markers in neocortical Brodmann area 9 (BA9) samples from 171 subjects with and without AD at different levels of cognitive impairment. The expression levels of vesicular glutamate transporters (VGLUT1&2), glutamate uptake site (EAAT2), post-synaptic density protein of 95 kD (PSD95), vesicular GABA/glycine transporter (VIAAT), somatostatin (som), synaptophysin and choline acetyl transferase (ChAT) were evaluated. VGLUT2 and EAAT2 were unaffected by dementia. The VGLUT1, PSD95, VIAAT, som, ChAT and synaptophysin expression levels significantly decreased as dementia progressed. The maximal decrease varied between 12% (synaptophysin) and 42% (som). VGLUT1 was more strongly correlated with dementia than all of the other markers (polyserial correlation = -0.41). Principal component analysis using these markers was unable to differentiate the CDR groups from one another. Therefore, the status of the major synaptic markers in BA9 does not seem to be linked to the cognitive status of AD patients. The findings of this study suggest that the loss of synaptic markers in BA9 is a late event that is only weakly related to AD dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Alzheimer Disease / metabolism*
  • Biomarkers / metabolism*
  • Choline O-Acetyltransferase / metabolism
  • Cognition / physiology*
  • Female
  • Glutamic Acid / metabolism
  • Humans
  • Male
  • Neurons / metabolism
  • Prefrontal Cortex / metabolism*
  • Synapses / metabolism*
  • Synaptophysin / metabolism
  • Vesicular Glutamate Transport Protein 1 / metabolism
  • Vesicular Inhibitory Amino Acid Transport Proteins / metabolism


  • Biomarkers
  • Synaptophysin
  • Vesicular Glutamate Transport Protein 1
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • vesicular GABA transporter
  • Glutamic Acid
  • Choline O-Acetyltransferase