Integrated proteomics reveals brain-based cerebrospinal fluid biomarkers in asymptomatic and symptomatic Alzheimer's disease.
Integrated proteomics reveals brain-based cerebrospinal fluid biomarkers in asymptomatic and symptomatic Alzheimer's disease.
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DOI：
10.1126/sciadv.aaz9360
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发表时间：
2020-10
期刊：
影响因子：
13.6
通讯作者：
Seyfried NT
中科院分区：
文献类型：
--
作者：
Higginbotham L;Ping L;Dammer EB;Duong DM;Zhou M;Gearing M;Hurst C;Glass JD;Factor SA;Johnson ECB;Hajjar I;Lah JJ;Levey AI;Seyfried NT
整合蛋白质组学分析鉴定与阿尔茨海默病中基于脑的病理生理学相关的CSF生物标志物组阿尔茨海默病（AD）缺乏反映其多种潜在病理生理学的蛋白质生物标志物，阻碍了诊断和治疗的进展。在这里，我们使用整合蛋白质组学来鉴定代表广泛AD病理生理学的脑脊液（CSF）生物标志物。多重质谱法在AD CSF和脑中分别鉴定了约3500和约12，000种蛋白质。脑蛋白质组的网络分析解决了44个生物多样性模块，其中15个与CSF蛋白质组重叠。这些重叠模块中的CSF AD标志物被分解为代表不同病理生理过程的五个蛋白质组。突触和代谢小组在AD脑中减少，但在CSF中增加，而脑和CSF中富含胶质细胞的髓鞘形成和免疫小组增加。在>500个额外的CSF样品中证实了组变化的一致性和疾病特异性。这些小组还确定了无症状AD中的生物亚群。总的来说，这些结果是朝着AD临床应用的基于网络的生物标志物工具迈出的有希望的一步。
Integrative proteomic analysis identifies CSF biomarker panels linked to brain-based pathophysiologies in Alzheimer’s disease. Alzheimer’s disease (AD) lacks protein biomarkers reflective of its diverse underlying pathophysiology, hindering diagnostic and therapeutic advancements. Here, we used integrative proteomics to identify cerebrospinal fluid (CSF) biomarkers representing a wide spectrum of AD pathophysiology. Multiplex mass spectrometry identified ~3500 and ~12,000 proteins in AD CSF and brain, respectively. Network analysis of the brain proteome resolved 44 biologically diverse modules, 15 of which overlapped with the CSF proteome. CSF AD markers in these overlapping modules were collapsed into five protein panels representing distinct pathophysiological processes. Synaptic and metabolic panels were decreased in AD brain but increased in CSF, while glial-enriched myelination and immunity panels were increased in brain and CSF. The consistency and disease specificity of panel changes were confirmed in >500 additional CSF samples. These panels also identified biological subpopulations within asymptomatic AD. Overall, these results are a promising step toward a network-based biomarker tool for AD clinical applications.
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影响因子：
4.2
作者：
Dinkins MB;Dasgupta S;Wang G;Zhu G;Bieberich E
通讯作者：
Bieberich E
影响因子：
16.2
作者：
Bai, Bing;Wang, Xusheng;Peng, Junmin
通讯作者：
Peng, Junmin
影响因子：
14.5
作者：
Bereczki, Erika;Branca, Rui M.;Aarsland, Dag
通讯作者：
Aarsland, Dag
影响因子：
4.8
作者：
Dai, Jingting;Johnson, Erik C. B.;Seyfried, Nicholas T.
通讯作者：
Seyfried, Nicholas T.
影响因子：
2.1
作者：
Driscoll, I.;Troncoso, J.
通讯作者：
Troncoso, J.