Oizumi Hideki, Hasegawa Takafumi, Kawahata Ichiro, Sekimori Tomoki, Totsune Tomoko, Sugimura Yoko, Baba Toru, Fukunaga Kohji, Takeda Atsushi
Department of Neurology, National Hospital Organization Sendai Nishitaga Hospital, 2-11-11, Kagitorihoncho, Taihaku-ku, Sendai, Miyagi 982-8555, Japan.
Department of Neurology, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
Clin Park Relat Disord. 2025 Mar 11;12:100313. doi: 10.1016/j.prdoa.2025.100313. eCollection 2025.
Early identification of the poor prognosis subtype by surrogate markers would be advantageous for selecting treatments for Parkinson's disease (PD). The aim of the present study was to test whether plasma neurofilament light chain (NF-L), total tau (t-tau), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), fatty acid-binding protein 3 (FABP3), and phosphorylated tau (p-tau) can be used as prognostic biomarkers in PD.
In the present study, both retrospective and prospective studies were performed. Plasma samples at baseline from 81 PD patients were included in the prospective study. Plasma samples at baseline from 60 patients who underwent cognitive assessment were subjected to the hierarchical cluster analysis for a retrospective study.
On the basis of the results of the cluster analysis, patients were classified into three groups: groups (G)1, G2 and G3. Individuals in the G1 cluster, who had an older age at onset and were prone to early progression with dementia, had significantly greater plasma NF-L levels than those in the G3 cluster, who did not present with dementia at an early stage. A Cox proportional hazards regression model adjusted for age and sex revealed that high NF-L and UCH-L1 levels at baseline predicted the four future milestones (i.e., nursing care, dysphagia, wheelchair use, and repeated falls), and high plasma t-tau at baseline predicted future dysphagia.
Although further studies with a larger number of patients will be required, plasma NF-L may be a useful biomarker for identifying the rapidly progressive subtype of PD, and plasma NF-L and UCH-L1 may serve as biomarkers of overall PD prognosis, whereas plasma t-tau could be a biomarker for future dysphagia in PD.
通过替代标志物早期识别帕金森病(PD)的预后不良亚型,将有助于选择治疗方案。本研究旨在测试血浆神经丝轻链(NF-L)、总tau蛋白(t-tau)、泛素羧基末端水解酶L1(UCH-L1)、脂肪酸结合蛋白3(FABP3)和磷酸化tau蛋白(p-tau)是否可作为PD的预后生物标志物。
在本研究中,进行了回顾性和前瞻性研究。前瞻性研究纳入了81例PD患者基线时的血浆样本。对60例接受认知评估患者基线时的血浆样本进行回顾性分层聚类分析。
根据聚类分析结果,患者被分为三组:第1组(G1)、第2组(G2)和第3组(G3)。G1组患者发病年龄较大,且易早期进展为痴呆,其血浆NF-L水平显著高于G3组患者,后者早期无痴呆表现。经年龄和性别校正的Cox比例风险回归模型显示,基线时高NF-L和UCH-L1水平可预测未来四个重要事件(即护理、吞咽困难、使用轮椅和反复跌倒),基线时高血浆t-tau水平可预测未来吞咽困难。
尽管需要对更多患者进行进一步研究,但血浆NF-L可能是识别PD快速进展亚型的有用生物标志物,血浆NF-L和UCH-L1可能作为PD总体预后的生物标志物,而血浆t-tau可能是PD未来吞咽困难的生物标志物。