Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson's disease.
Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson's disease.
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DOI：
10.1186/s12974-017-0935-1
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发表时间：
2017-08-18
影响因子：
9.3
通讯作者：
Tansey MG
中科院分区：
文献类型：
--
作者：
Eidson LN;Kannarkat GT;Barnum CJ;Chang J;Chung J;Caspell-Garcia C;Taylor P;Mollenhauer B;Schlossmacher MG;Ereshefsky L;Yen M;Kopil C;Frasier M;Marek K;Hertzberg VS;Tansey MG
在过去的十年中，识别帕金森病（PD）的流体生物标志物的努力已经加强。随着炎症在PD病理生理学中的作用越来越被认识到，研究人员旨在定义炎症特征，以帮助阐明疾病发病机制的潜在机制，并帮助识别可能受益于免疫调节干预的炎症内表型患者。然而，文献中不一致的结果和缺乏关于24小时内炎症因子稳定性的信息阻碍了进展。在这里，我们在24小时内的11个时间点测量了一小群PD（n = 12）和年龄匹配的健康对照（HC）受试者（n = 6）的血清和CSF中的炎症蛋白，以（1）确定潜在的昼夜变化，（2）揭示PD与HC的差异，和（3）与CSF中淀粉样蛋白β（Aβ）和α-突触核蛋白水平相关，以产生关于PD候选生物标志物的数据驱动假设。尽管其他因素存在显著变异性，但按时间和疾病状态对每种分析物进行的重复测量双向方差分析显示，血清IFNγ、TNF和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）在24小时内保持稳定，HC和PD之间存在差异。回归分析显示，C反应蛋白（CRP）是唯一的因素与CSF和血清之间的强线性关系。PD和HC患者CSF Aβ蛋白和α-synuclein与特异性炎症因子的关系存在显著差异，CSF IFNγ和血清IL-8与PD的临床指标呈正相关。最后，线性判别分析显示，血清TNF和CSF α-突触核蛋白区分PD和HC的灵敏度最低为82%，特异性为83%。我们的研究结果确定了血清和CSF中的一组炎症因子，可以可靠地测量，区分PD和HC，并随着疾病进展或对介入治疗的反应监测炎症。该小组可以通过关注无论样本采集时间如何都保持稳定的分析物来帮助产生假设和可行的实验设计，以鉴定神经退行性疾病的生物标志物。本文的在线版本（doi：10.1186/s12974-017-0935-1）包含补充材料，可供授权用户使用。
Efforts to identify fluid biomarkers of Parkinson’s disease (PD) have intensified in the last decade. As the role of inflammation in PD pathophysiology becomes increasingly recognized, investigators aim to define inflammatory signatures to help elucidate underlying mechanisms of disease pathogenesis and aid in identification of patients with inflammatory endophenotypes that could benefit from immunomodulatory interventions. However, discordant results in the literature and a lack of information regarding the stability of inflammatory factors over a 24-h period have hampered progress. Here, we measured inflammatory proteins in serum and CSF of a small cohort of PD (n = 12) and age-matched healthy control (HC) subjects (n = 6) at 11 time points across 24 h to (1) identify potential diurnal variation, (2) reveal differences in PD vs HC, and (3) to correlate with CSF levels of amyloid β (Aβ) and α-synuclein in an effort to generate data-driven hypotheses regarding candidate biomarkers of PD. Despite significant variability in other factors, a repeated measures two-way analysis of variance by time and disease state for each analyte revealed that serum IFNγ, TNF, and neutrophil gelatinase-associated lipocalin (NGAL) were stable across 24 h and different between HC and PD. Regression analysis revealed that C-reactive protein (CRP) was the only factor with a strong linear relationship between CSF and serum. PD and HC subjects showed significantly different relationships between CSF Aβ proteins and α-synuclein and specific inflammatory factors, and CSF IFNγ and serum IL-8 positively correlated with clinical measures of PD. Finally, linear discriminant analysis revealed that serum TNF and CSF α-synuclein discriminated between PD and HC with a minimum of 82% sensitivity and 83% specificity. Our findings identify a panel of inflammatory factors in serum and CSF that can be reliably measured, distinguish between PD and HC, and monitor inflammation as disease progresses or in response to interventional therapies. This panel may aid in generating hypotheses and feasible experimental designs towards identifying biomarkers of neurodegenerative disease by focusing on analytes that remain stable regardless of time of sample collection. The online version of this article (doi:10.1186/s12974-017-0935-1) contains supplementary material, which is available to authorized users.
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影响因子：
9.3
作者：
Brockmann K;Apel A;Schulte C;Schneiderhan-Marra N;Pont-Sunyer C;Vilas D;Ruiz-Martinez J;Langkamp M;Corvol JC;Cormier F;Knorpp T;Joos TO;Gasser T;Schüle B;Aasly JO;Foroud T;Marti-Masso JF;Brice A;Tolosa E;Marras C;Berg D;Maetzler W
通讯作者：
Maetzler W
影响因子：
4.8
作者：
Felger, Jennifer C.;Hernandez, Carla R.;Miller, Andrew H.
通讯作者：
Miller, Andrew H.
DOI：
10.3233/jpd-140410
发表时间：
2014
期刊：
Journal of Parkinson's disease
影响因子：
--
作者：
Barnum CJ;Chen X;Chung J;Chang J;Williams M;Grigoryan N;Tesi RJ;Tansey MG
通讯作者：
Tansey MG
DOI：
10.1006/neur.1996.0020
发表时间：
1996-06-01
期刊：
NEURODEGENERATION
影响因子：
--
作者：
Czlonkowska, A;Kohutnicka, M;Czlonkowski, A
通讯作者：
Czlonkowski, A
影响因子：
2.5
作者：
BOKA, G;ANGLADE, P;HIRSCH, EC
通讯作者：
HIRSCH, EC