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The synaptic proteome in Alzheimer's disease
Author(s) -
Chang Rachel Yoon Kyung,
Nouwens Amanda S.,
Dodd Peter R.,
Etheridge Naomi
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.04.009
Subject(s) - synapse , proteome , neuroscience , synaptic vesicle , hippocampus , dementia , vascular dementia , biology , alzheimer's disease , chemistry , disease , medicine , pathology , bioinformatics , biochemistry , vesicle , membrane
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.