Xu Fang, Huang Hongyan, Feng Jiaming, Shen Qiuyan, Bao Yi, Zhang Dan, Xu Yanming
Department of Neurology, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Chengdu, Sichuan, 610041, China.
West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
J Neurol. 2024 Dec 16;272(1):61. doi: 10.1007/s00415-024-12856-6.
To explore whether CSF phosphorylated tau-181 (P-tau181) and total tau (T-tau) are associated with disease progression in early PD patients.
We analyzed 8-year longitudinal clinical data from 368 early, drug-naive PD patients and 185 matched controls from the Parkinson's Progression Markers Initiative cohort. CSF P-tau181 and T-tau were measured over 5 years, while CSF α-synuclein was measured over 3 years. Dopamine transporter (DAT) imaging was performed at baseline and at 1, 2, and 4 years.
PD patients exhibited significantly lower CSF P-tau181, T-tau and P-tau181/T-tau ratio than controls at each visit. Higher baseline CSF P-tau181 predicted greater increases in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III (estimate: 0.067, P < 0.001) and Montreal Cognitive Assessment (MoCA) scores (estimate: -0.010, P = 0.009). Similarly, higher baseline CSF T-tau predicted greater increases in MDS-UPDRS III (estimate: 0.005, P < 0.001) and MoCA scores (estimate: -0.001, P = 0.013). Higher baseline P-tau181/T-tau ratio predicted greater increases in MDS-UPDRS III (estimate: 0.552, P < 0.001) but was not significantly associated with changes in MoCA scores (estimate: -0.052, P = 0.114). CSF P-tau181 (estimate = 84.889, P < 0.001), T-tau (estimate = 8.297, P < 0.001) and P-tau181/T-tau ratio (estimate = 263.425, P < 0.001) were positively correlated with CSF α-synuclein but not correlated with striatal DAT uptake.
Elevated baseline CSF P-tau181, T-tau and P-tau181/T-tau ratio in early PD patients predict accelerated motor deterioration, with P-tau181 and T-tau also predicting cognitive decline, potentially through interactions with α-synuclein. However, the direct role of tau on nigrostriatal dopaminergic degeneration remains uncertain.
探讨脑脊液磷酸化tau-181（P-tau181）和总tau（T-tau）是否与早期帕金森病（PD）患者的疾病进展相关。
我们分析了帕金森病进展标志物计划队列中368例早期未用药的PD患者和185例匹配对照的8年纵向临床数据。在5年时间里测量脑脊液P-tau181和T-tau，在3年时间里测量脑脊液α-突触核蛋白。在基线以及第1、2和4年进行多巴胺转运体（DAT）成像。
每次随访时，PD患者的脑脊液P-tau181、T-tau和P-tau181/T-tau比值均显著低于对照组。较高的基线脑脊液P-tau181预示着运动障碍协会统一帕金森病评定量表（MDS-UPDRS）III评分（估计值：0.067，P<0.001）和蒙特利尔认知评估（MoCA）评分有更大幅度的增加（估计值：-0.010，P=0.009）。同样，较高的基线脑脊液T-tau预示着MDS-UPDRS III评分（估计值：0.005，P<0.001）和MoCA评分有更大幅度的增加（估计值：-0.001，P=0.013）。较高的基线P-tau181/T-tau比值预示着MDS-UPDRS III评分有更大幅度的增加（估计值：0.552，P<0.001），但与MoCA评分的变化无显著相关性（估计值：-0.052，P=0.114）。脑脊液P-tau181（估计值=84.889，P<0.001）、T-tau（估计值=8.297，P<0.001）和P-tau181/T-tau比值（估计值=263.425，P<0.001）与脑脊液α-突触核蛋白呈正相关，但与纹状体DAT摄取无相关性。
早期PD患者基线脑脊液P-tau181、T-tau和P-tau181/T-tau比值升高预示着运动功能加速恶化，P-tau181和T-tau还预示着认知功能下降，可能是通过与α-突触核蛋白相互作用。然而，tau在黑质纹状体多巴胺能变性中的直接作用仍不确定。
