The synaptic proteome in Alzheimer's disease

Chang, Rachel Yoon Kyung, Nouwens, Amanda S., Dodd, Peter R. and Etheridge, Naomi (2013) The synaptic proteome in Alzheimer's disease. Alzheimer's & Dementia, 9 5: 499-511. doi:10.1016/j.jalz.2012.04.009

Author Chang, Rachel Yoon Kyung
Nouwens, Amanda S.
Dodd, Peter R.
Etheridge, Naomi
Title The synaptic proteome in Alzheimer's disease
Journal name Alzheimer's & Dementia   Check publisher's open access policy
ISSN 1552-5260
Publication date 2013-09
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.jalz.2012.04.009
Volume 9
Issue 5
Start page 499
End page 511
Total pages 13
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Collection year 2013
Language eng
Formatted abstract
Background: Synaptic dysfunction occurs early in Alzheimer's disease (AD) and is recognized to be a primary pathological target for treatment. Synapse degeneration or dysfunction contributes to clinical signs of dementia through altered neuronal communication; the degree of synaptic loss correlates strongly with cognitive impairment. The molecular mechanisms underlying synaptic degeneration are still unclear, and identifying abnormally expressed synaptic proteins in AD brain will help to elucidate such mechanisms and to identify therapeutic targets that might slow AD progression.

Methods: Synaptosomal fractions from human autopsy brain tissue from subjects with AD (n = 6) and without AD (n = 6) were compared using two-dimensional differential in-gel electrophoresis. AD pathology is region specific; human subjects can be highly variable in age, medication, and other factors. To counter these factors, two vulnerable areas (the hippocampus and the temporal cortex) were compared with two relatively spared areas (the motor and occipital cortices) within each group. Proteins exhibiting significant changes in expression were identified (≥20% change, Newman-Keuls P value < .05) using either matrix-assisted laser desorption ionization time-of-flight or electrospray ionisation quadrupole-time of flight mass spectrometry.

Results: Twenty-six different synaptic proteins exhibited more than twofold differences in expression between AD and normal subjects. These proteins are involved in regulating different cellular functions, including energy metabolism, signal transduction, vesicle transport, structure, and antioxidant activity.

Conclusion: Comparative proteome analysis uncovered markers of pathogenic mechanisms involved in synaptic dysfunction.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online: 13 November 2012.

Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 12 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 23 Nov 2012, 10:04:44 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences