Multi-platform proteomic analysis of Alzheimer's disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisome.
Multi-platform proteomic analysis of Alzheimer's disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisome.
复制标题
DOI：
10.1186/s13195-022-01113-5
复制
发表时间：
2022-11-17
影响因子：
9
通讯作者：
Johnson, Erik C. B.
中科院分区：
文献类型：
--
作者：
Dammer, Eric B.;Ping, Lingyan;Duong, Duc M.;Modeste, Erica S.;Seyfried, Nicholas T.;Lah, James J.;Levey, Allan, I;Johnson, Erik C. B.
迫切需要能够捕获阿尔茨海默病及其多种病理过程的异质性的强大且可获得的生物标志物。在这里，我们进行了调查阿尔茨海默氏病脑脊液（CSF）和血浆从相同的主题（n=18控制，n=18 AD）使用三种不同的蛋白质组学平台SomaLogic SomaScan，Olink邻近延伸分析，和串联质谱标记为基础的质谱，以评估这两种生物液体中的蛋白质标记物可能作为可靠的生物标志物的AD病理生理学观察无偏见的脑蛋白质组学研究。CSF（r~0.7）和血浆（r~0.6）中平台间重叠蛋白测量值的中位相关性良好，血浆中的变异性更大。SomaScan技术在血浆中提供了最多的测量。令人惊讶的是，发现在AD CSF中改变的许多蛋白质在血浆中以相反的方向改变，包括AD脑共表达模块的重要成员。一个例外是SMOC 1，它是与AD中淀粉样蛋白-β沉积相关的脑基质体模块的关键成员，发现其在CSF和血浆中均升高。在所有蛋白质组学平台上，对CSF中超过7000个蛋白质测量值和血浆中9500个蛋白质测量值的蛋白质共表达分析揭示了与CSF中的自噬、泛素化和糖代谢以及血浆中的内吞和基质体相关的模块的强烈变化。跨平台和跨生物流体蛋白质组学代表了AD生物标志物开发的一种有前途的方法。在线版本包含补充材料，可通过10.1186/s13195-022-01113-5获得。
Robust and accessible biomarkers that can capture the heterogeneity of Alzheimer’s disease and its diverse pathological processes are urgently needed. Here, we undertook an investigation of Alzheimer’s disease cerebrospinal fluid (CSF) and plasma from the same subjects (n=18 control, n=18 AD) using three different proteomic platforms—SomaLogic SomaScan, Olink proximity extension assay, and tandem mass tag-based mass spectrometry—to assess which protein markers in these two biofluids may serve as reliable biomarkers of AD pathophysiology observed from unbiased brain proteomics studies. Median correlation of overlapping protein measurements across platforms in CSF (r~0.7) and plasma (r~0.6) was good, with more variability in plasma. The SomaScan technology provided the most measurements in plasma. Surprisingly, many proteins altered in AD CSF were found to be altered in the opposite direction in plasma, including important members of AD brain co-expression modules. An exception was SMOC1, a key member of the brain matrisome module associated with amyloid-β deposition in AD, which was found to be elevated in both CSF and plasma. Protein co-expression analysis on greater than 7000 protein measurements in CSF and 9500 protein measurements in plasma across all proteomic platforms revealed strong changes in modules related to autophagy, ubiquitination, and sugar metabolism in CSF, and endocytosis and the matrisome in plasma. Cross-platform and cross-biofluid proteomics represents a promising approach for AD biomarker development. The online version contains supplementary material available at 10.1186/s13195-022-01113-5.
登录
查看更多内容
影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
影响因子：
25
作者：
Mostafavi S;Gaiteri C;Sullivan SE;White CC;Tasaki S;Xu J;Taga M;Klein HU;Patrick E;Komashko V;McCabe C;Smith R;Bradshaw EM;Root DE;Regev A;Yu L;Chibnik LB;Schneider JA;Young-Pearse TL;Bennett DA;De Jager PL
通讯作者：
De Jager PL
DOI：
10.3233/jad-200948
发表时间：
2021
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Birkenbihl C;Westwood S;Shi L;Nevado-Holgado A;Westman E;Lovestone S;AddNeuroMed Consortium;Hofmann-Apitius M
通讯作者：
Hofmann-Apitius M
影响因子：
25
作者：
Johnson ECB;Carter EK;Dammer EB;Duong DM;Gerasimov ES;Liu Y;Liu J;Betarbet R;Ping L;Yin L;Serrano GE;Beach TG;Peng J;De Jager PL;Haroutunian V;Zhang B;Gaiteri C;Bennett DA;Gearing M;Wingo TS;Wingo AP;Lah JJ;Levey AI;Seyfried NT
通讯作者：
Seyfried NT
影响因子：
16.2
作者：
Bai, Bing;Wang, Xusheng;Peng, Junmin
通讯作者：
Peng, Junmin