Proteomic analysis of postsynaptic density in Alzheimer's Disease

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• 作者：Jianying Zhou ; Drew R. Jones ; Duc M. Duong ; Allan I. Levey ; James J. Lah ; Junmin Peng ; ^{junmin.peng@stjude.org}
• 关键词：Alzheimer's Disease ; Proteomics ; Mass spectrometry ; Synapse
• 刊名：Clinica Chimica Acta
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：420
• 期：Complete
• 页码：62-68
• 全文大小：452 K

文摘

Background

The loss of synaptic function is a pivotal mechanism in the development of Alzheimer's Disease (AD). Structural changes and loss of plasticity in the postsynaptic density (PSD) may contribute to the pathogenesis. However, the underlying molecular events triggering synaptic dysfunction remain elusive. We report a quantitative proteomic analysis of the PSD from human postmortem brain tissues of possible and definite AD cases.

Methods

The analysis used both discovery and targeted mass spectrometry approaches and was repeated with biological replicates. During the discovery study, we compared several hundred proteins in the PSD-enriched fractions and found that 25 proteins were differentially regulated in AD.

Results

Interestingly, the majority of these protein changes were larger in definite AD cases than in possible AD cases. In the targeted analysis, we measured the level of 9 core PSD proteins and found that only IRSp53 was highly down-regulated in AD. The alteration of selected proteins (i.e. internexin and IRSp53) was further validated by immunoblotting against 7 control and 8 AD cases.

Conclusions

These results expand our understanding of how AD impacts PSD composition, and hints at new hypotheses for AD pathogenesis.