Insights into the changes in the proteome of Alzheimer disease elucidated by a meta-analysis.
Insights into the changes in the proteome of Alzheimer disease elucidated by a meta-analysis.
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DOI：
10.1038/s41597-021-01090-8
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发表时间：
2021-12-03
期刊：
影响因子：
9.8
通讯作者：
Tjernberg LO
中科院分区：
文献类型：
--
作者：
Haytural H;Benfeitas R;Schedin-Weiss S;Bereczki E;Rezeli M;Unwin RD;Wang X;Dammer EB;Johnson ECB;Seyfried NT;Winblad B;Tijms BM;Visser PJ;Frykman S;Tjernberg LO
基于质谱技术的蛋白质组学是一种无偏地探索疾病致病变化的有力工具，已被广泛应用于阿尔茨海默病（AD）的研究。在这里，通过对高质量的蛋白质组学研究进行荟萃分析，我们解决了哪些病理变化是一致观察到的，因此最有可能对AD发病机制非常重要。我们检索了数据集，包括在857个死后人类样本中鉴定的21，588种不同的蛋白质，这些蛋白质来自10项使用标记或无标记MS方法的研究。我们的荟萃分析结果显示，在标记和无标记数据集中，AD中分别有757和1，195个蛋白质发生了显著变化。只有33种蛋白质，其中一些与突触信号相关，在各个研究中具有相同的方向变化。然而，尽管在标记和无标记数据集之间个体蛋白质的改变不同，但与突触信号传导、氧化磷酸化、免疫应答和细胞外基质相关的几种途径在AD中通常失调。这些途径代表了人类AD大脑的强大变化，值得进一步研究。
Mass spectrometry (MS)-based proteomics is a powerful tool to explore pathogenic changes of a disease in an unbiased manner and has been used extensively in Alzheimer disease (AD) research. Here, by performing a meta-analysis of high-quality proteomic studies, we address which pathological changes are observed consistently and therefore most likely are of great importance for AD pathogenesis. We retrieved datasets, comprising a total of 21,588 distinct proteins identified across 857 postmortem human samples, from ten studies using labeled or label-free MS approaches. Our meta-analysis findings showed significant alterations of 757 and 1,195 proteins in AD in the labeled and label-free datasets, respectively. Only 33 proteins, some of which were associated with synaptic signaling, had the same directional change across the individual studies. However, despite alterations in individual proteins being different between the labeled and the label-free datasets, several pathways related to synaptic signaling, oxidative phosphorylation, immune response and extracellular matrix were commonly dysregulated in AD. These pathways represent robust changes in the human AD brain and warrant further investigation.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
影响因子：
14
作者：
Bereczki, Erika;Francis, Paul T.;Aarsland, Dag
通讯作者：
Aarsland, Dag
影响因子：
16.2
作者：
Bai, Bing;Wang, Xusheng;Peng, Junmin
通讯作者：
Peng, Junmin
影响因子：
7
作者：
Haytural, Hazal;Mermelekas, Georgios;Frykman, Susanne
通讯作者：
Frykman, Susanne