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

Alzheimer's & Dementia - Tập 15 - Trang 429-440 - 2019
Feng Xiong1, Wei Ge1, Chao Ma2
1State Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
2Department of Human Anatomy, Histology and Embryology, Neuroscience Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China

Tóm tắt

AbstractIntroductionWe 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.MethodsAPs 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.ResultsOver 4000 proteins were accurately quantified, and more than 40 were identified as highly enriched in both AD and non‐AD APs, including apoE, midkine, VGFR1, and complement C4. Intriguingly, proteins including synaptic structural proteins and complement C1r, C5, and C9 were found to be upregulated in AD APs but not non‐AD APs. Moreover, the proteomic pattern of AD APs was distinct from APP/PS1 APs and exhibited correlation with aging hippocampus.DiscussionOur results provide new insight into AP composition. We demonstrate unexpected differences between AD, non‐AD, and APP/PS1 mouse APs, which may relate to different pathological processes.

Tài liệu tham khảo

10.1016/j.neuron.2014.05.004 10.1016/j.cell.2012.02.040 10.15252/emmm.201606210 10.1038/nature06616 10.1038/nrm2101 10.1038/nm1782 10.1186/alzrt269 10.1038/nrneurol.2014.44 10.1038/nrneurol.2012.236 10.1073/pnas.0914257107 10.1212/01.wnl.0000219668.47116.e6 10.1001/archneur.65.11.1509 10.1016/j.jalz.2011.03.003 10.1111/j.1749-6632.2000.tb05554.x 10.1126/science.aad0189 10.1038/nn.4160 10.3233/JAD-2007-11203 10.1021/pr401202d Hadley KC, 2015, Determining composition of micron‐scale protein deposits in neurodegenerative disease by spatially targeted optical microproteomics, Elife, 4, 10.7554/eLife.09579 10.1016/j.jalz.2015.11.002 10.1074/jbc.M403672200 10.1007/s00401-017-1691-0 10.1016/j.neurobiolaging.2015.11.029 10.1074/jbc.M508125200 10.1093/nar/gkq1039 10.1038/srep11138 10.1021/pr200987h 10.1016/j.ymeth.2015.11.007 10.1073/pnas.0930122100 10.1007/s00216-012-6203-4 10.1038/sj.emboj.7601051 10.1126/science.1161748 10.1074/jbc.M113.511212 10.1016/j.bcp.2014.01.008 10.1212/WNL.49.1.56 10.1016/j.neuron.2004.07.017 10.1016/j.exger.2015.11.016 10.1101/cshperspect.a006346 10.1016/j.cell.2007.10.036 10.1523/JNEUROSCI.0829-08.2008 10.1126/science.aad8373 10.1073/pnas.0811698106 10.1073/pnas.1214718110 10.1016/j.neuron.2007.05.029 10.1016/j.mcn.2011.05.009 10.1007/s00216-012-6261-7 10.1006/bbrc.1993.1406 10.3233/JAD-150318 10.1038/cdd.2008.191 10.1016/0092-8674(88)90462-X 10.1002/pmic.200700145 10.1523/JNEUROSCI.18-18-07061.1998
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Alzheimer's & Dementia

Tập 15

429-440

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