在患有渐进性超核性麻的患者中,CSF蛋白质组
Amy Wise1, Jingyao Li1, Mai Yamakawa1
1From the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.
这项研究使用aptamer蛋白质组学确定了渐进性上核麻 (PSP) 的新型脑脊液 (CSF) 生物标志物. 在PSP中,Axon引导通路蛋白被显著下调,为未来的诊断和治疗提供了潜在的点.
科学领域:
- 神经科学是一个神经科学.
- 蛋白质组学是指蛋白质组学.
- 生物标志物发现发现
背景情况:
- 渐进性超核性 (PSP) 缺乏确定的液体生物标志物,阻碍了治疗的发展.
- 基于无偏向的阿普坦蛋白质组学被用来发现PSP的CSF中的新生物标志物.
研究的目的:
- 识别和验证新型脑脊液 (CSF) 蛋白质生物标志物,用于逐渐超核性麻 (PSP).
- 探索已识别的生物标志物的诊断实用性和与疾病严重程度的关联.
主要方法:
- 在临床诊断的PSP和健康对照的CSF样本上使用DNA合体 (SOMAmer) 蛋白质组的横截面研究.
- 通过使用SomaScan平台对三个队列进行分析:原始,验证和神经病理学证实.
- 统计分析包括差异表达,途径丰富,共表达网络分析,ROC曲线和临床严重程度相关性的线性回归.
主要成果:
- 多个SOMAmers在PSP队列中表现出差异性表达,大多数显示信号减少.
- 突触功能/JAK-STAT,囊泡细胞骨贩运和细胞因子-细胞因子受体相互作用途径与PSP有关.
- 在所有队列中,PSP显著下调了轴突引导通路蛋白,并显示出高诊断准确性 (AUC > 0.815).
- 两个炎症蛋白质,加勒-10和CTLA-4,与PSP临床严重性得分相关.
结论:
- 轴突引导通路蛋白和其他分子通路的下调是PSP的特征.
- 这些蛋白质代表了PSP生物标志物和治疗开发的有希望的候选人.
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