Proteomics

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Quantitative proteomic characterization of senile plaques from Alzheimer's disease and non-demented brain


ABSTRACT: The deposition of amyloid senile plaques (SPs) play a central role in Alzheimer’s disease (AD), but the mechanisms by which SPs induce neural toxicity are disputed. Genetically engineered mouse models emphasising SPs have had limited success in reproducing the neuropathology of AD, and have also failed to be good indicators of successful amyloid-targeting therapies. Moreover, elderly people with a heavy plaque burden can show normal cognition. Therefore, it is fundamentally important to fully characterize and distinguish the pathological changes elicited by SPs in human and mouse brains. Using laser capture microdissection (LCM) combined with high-throughput mass spectrometry, we quantified ~5000 proteins with high confidence in SPs and non-plaque regions from AD and non-AD human postmortem brain. We found proteomic alteration in SPs is more evident than in non-plaque regions, and identified more than 30 human that are significantly enriched in SPs. We found that AD SPs elicited much more extensive proteomic alterations compared to non-AD SPs. Together, our findings represent the most systematic analysis of sub-proteome of senile plaques and provide a framework for future studies on plaque pathology and AD progression.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo sapiens  

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: Wei Ge  

LAB HEAD: Wei Ge

PROVIDER: PXD005824 | Pride | 2019-02-18

REPOSITORIES: pride

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Publications

Quantitative proteomics reveals distinct composition of amyloid plaques in Alzheimer's disease.

Xiong Feng F   Ge Wei W   Ma Chao C  

Alzheimer's & dementia : the journal of the Alzheimer's Association 20190102 3


INTRODUCTION:We investigated the proteomic profiles of amyloid plaques (APs) from Alzheimer's disease (AD) and age-matched non-AD brains and APP/PS1 transgenic model mice. METHODS:APs and adjacent control regions were collected from fresh-frozen brain sections using laser capture dissection. Proteins were quantitated using tag-labeling coupled high-throughput mass spectra. RESULTS:Over 4000 proteins were accurately quantified, and more than 40 were identified as highly enriched in both AD and no  ...[more]

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