组织因子及其在帕金森病中的脑脊液蛋白谱。
Tissue Factor and Its Cerebrospinal Fluid Protein Profiles in Parkinson's Disease.
机构信息
Center of Neurology, Department of Neurodegeneration and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tübingen, Germany.
German Center for Neurodegenerative Diseases (DZNE), University of Tuebingen, Tübingen, Germany.
出版信息
J Parkinsons Dis. 2024;14(7):1405-1416. doi: 10.3233/JPD-240115.
BACKGROUND
Prior investigations have elucidated pathophysiological interactions involving blood coagulation and neurodegenerative diseases. These interactions pertain to age-related effects and a mild platelet antiaggregant function of exogenous α-Synuclein.
OBJECTIVE
Our study sought to explore whether cerebrospinal fluid (CSF) levels of tissue factor (TF), the initiator of the extrinsic pathway of hemostasis, differ between controls (CON) compared to patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB), considering that these conditions represent a spectrum of α-Synuclein pathology. We further investigated whether TF levels are associated with longitudinal progression in PD.
METHODS
We examined CSF levels of TF in 479 PD patients, 67 patients diagnosed with DLB, and 16 CON in order to evaluate potential continuum patterns among DLB, PD, and CON. Of the 479 PD patients, 96 carried a GBA1 variant (PD GBA1), while the 383 non-carriers were classified as PD wildtype (PD WT). We considered both longitudinal clinical data as well as CSF measurements of common neurodegenerative markers (amyloid-β 1-42, h-Tau, p-Tau, NfL, α-Synuclein). Kaplan-Meier survival and Cox regression analysis stratified by TF tertile levels was conducted.
RESULTS
Higher CSF levels of TF were associated with an older age at examination in PD and a significant later onset of postural instability in PD GBA1. TF levels were lower in male vs. female PD. DLB GBA1 exhibited the lowest TF levels, followed by PD GBA1, with CON showing the highest levels.
CONCLUSIONS
TF as representative of blood hemostasis could be an interesting CSF candidate to further explore in PD and DLB.
背景
先前的研究已经阐明了涉及血液凝固和神经退行性疾病的病理生理相互作用。这些相互作用与年龄相关的影响以及外源性α-突触核蛋白的轻度血小板抗聚集功能有关。
目的
我们的研究旨在探讨组织因子（TF），即血液外源性凝血途径的启动因子，在对照组（CON）与帕金森病（PD）和路易体痴呆（DLB）患者之间的脑脊液（CSF）水平是否存在差异，因为这些疾病代表了α-突触核蛋白病理学的一个谱系。我们进一步研究了 TF 水平是否与 PD 的纵向进展有关。
方法
我们检查了 479 名 PD 患者、67 名 DLB 患者和 16 名 CON 的 CSF 中 TF 的水平，以评估 DLB、PD 和 CON 之间的潜在连续模式。在 479 名 PD 患者中，96 名携带 GBA1 变异（PD GBA1），而 383 名非携带者被归类为 PD 野生型（PD WT）。我们考虑了纵向临床数据以及常见神经退行性标志物（淀粉样β 1-42、h-Tau、p-Tau、NfL、α-突触核蛋白）的 CSF 测量值。进行了 Kaplan-Meier 生存分析和按 TF 三分位水平分层的 Cox 回归分析。
结果
在 PD 中，CSF 中 TF 水平较高与检查时年龄较大有关，在 PD GBA1 中与姿势不稳的发病时间较晚有关。PD 中男性的 TF 水平低于女性。DLB GBA1 的 TF 水平最低，其次是 PD GBA1，CON 的 TF 水平最高。
结论
作为血液止血的代表，TF 可能是 PD 和 DLB 中进一步探索的一个有趣的 CSF 候选物。
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