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Mol Cell Proteomics. 2016 Jul;15(7):2252-62. doi: 10.1074/mcp.M115.056580. Epub 2016 Apr 21.

Apolipoprotein E*4 (APOE*4) Genotype Is Associated with Altered Levels of Glutamate Signaling Proteins and Synaptic Coexpression Networks in the Prefrontal Cortex in Mild to Moderate Alzheimer Disease.

Author information

1
From the Departments of ‡Psychiatry, **Neurology, and ‡‡VISN 4 Mental Illness Research, Education and Clinical Center (MIRECC) and sweetra@upmc.edu.
2
From the Departments of ‡Psychiatry.
3
§Biostatistics.
4
¶Cell Biology.
5
‖Pathology.
6
**Neurology, and §§Geriatric Research, Education and Clinical Center (GRECC), VA Pittsburgh Healthcare System, Pittsburgh, PA.
7
From the Departments of ‡Psychiatry, **Neurology, and.
8
¶¶Environmental & Occupational Health, University of Pittsburgh, Pittsburgh, PA;

Abstract

It has been hypothesized that Alzheimer disease (AD) is primarily a disorder of the synapse. However, assessment of the synaptic proteome in AD subjects has been limited to a small number of proteins and often included subjects with end-stage pathology. Protein from prefrontal cortex gray matter of 59 AD subjects with mild to moderate dementia and 12 normal elderly subjects was assayed using targeted mass spectrometry to quantify 191 synaptically expressed proteins. The profile of synaptic protein expression clustered AD subjects into two groups. One of these was characterized by reduced expression of glutamate receptor proteins, significantly increased synaptic protein network coexpression, and associated withApolipoprotein E*4 (APOE*4) carrier status. The second group, by contrast, showed few differences from control subjects. A subset of AD subjects had altered prefrontal cortex synaptic proteostasis for glutamate receptors and their signaling partners. Efforts to therapeutically target glutamate receptors in AD may have outcomes dependent on APOE*4 genotype.

PMID:
27103636
PMCID:
PMC4937502
DOI:
10.1074/mcp.M115.056580
[Indexed for MEDLINE]
Free PMC Article

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