Differential expression of synaptic proteins in the frontal and temporal cortex of elderly subjects with mild cognitive impairment.


Journal Article

Alterations in synaptic protein stoichiometry may contribute to neocortical synaptic dysfunction in Alzheimer disease (AD). Whether perturbations in synaptic protein expression occur during the earliest stages of cognitive decline remain unclear. We examined protein levels of synaptophysin (SYP), synaptotagmin (SYT), and drebrin (DRB) in 5 neocortical regions (anterior cingulate, superior frontal, superior temporal, inferior parietal, and visual) of people clinically diagnosed with no cognitive impairment (NCI), mild cognitive impairment (MCI), mild/moderate AD, or severe AD. Normalized SYP levels were decreased approximately 35% in the superior temporal and inferior parietal cortex in severe AD compared with NCI. SYT levels were unchanged across clinical diagnosis in the cortical regions. Levels of DRB, a dendritic spine plasticity marker, were reduced approximately 40% to 60% in all cortical regions in AD compared with NCI. DRB protein was also reduced approximately 35% in the superior temporal cortex of MCI subjects, and DRB and SYP levels in the superior temporal cortex correlated with Mini-Mental State Examination and Braak scores. In contrast, DRB levels in the superior frontal cortex increased approximately 30% in MCI subjects. The differential changes in DRB expression in the frontal and temporal cortex in MCI suggest a disparity of dendritic plasticity within these regions that may contribute to the early impairment of temporal cortical functions subserving memory and language compared with the relative preservation of frontal cortical executive function during the initial stages of cognitive decline.

Full Text

Duke Authors

Cited Authors

  • Counts, SE; Nadeem, M; Lad, SP; Wuu, J; Mufson, EJ

Published Date

  • June 2006

Published In

Volume / Issue

  • 65 / 6

Start / End Page

  • 592 - 601

PubMed ID

  • 16783169

Pubmed Central ID

  • 16783169

International Standard Serial Number (ISSN)

  • 0022-3069

Digital Object Identifier (DOI)

  • 10.1097/00005072-200606000-00007


  • eng

Conference Location

  • England