背景:已证明反应性星形胶质细胞增生在帕金森病(PD)中起作用;然而,星形胶质细胞特异性血浆胶质纤维酸性蛋白(GFAP)与PD进展的相关性尚不清楚。我们旨在确定血浆GFAP是否可以监测和预测PD进展。
方法:本前瞻性队列研究共纳入184例PD患者和95例健康对照(HCs),并随访5年。血浆GFAP,淀粉样β(Aβ),在基线和1年和2年随访时测量p-tau181和神经丝轻链(NfL)。运动和非运动症状,日常生活活动,全局认知功能,执行功能,和疾病阶段使用统一帕金森病评定量表(UPDRS)第三部分进行评估,UPDRS-I,UPDRS-II,蒙特利尔认知评估(MoCA)正面评估电池(FAB),每次访问时,Hoehn和Yahr(H&Y)量表,分别。
结果:PD患者的血浆GFAP水平较高(平均值[SD]:69.80[36.18],pg/mL)与HC(平均值[SD]:57.89[23.54],pg/mL)。在女性和老年PD患者中观察到较高水平的GFAP。调整后的线性混合效应模型显示血浆GFAP水平与UPDRS-I评分显著相关(β:0.006,95%CI[0.001-0.011],p=0.027)。较高的基线血浆GFAP与UPDRS-I的更快增加相关(β:0.237,95%CI[0.055-0.419],p=0.011)和UPDRS-III(β:0.676,95%CI[0.023-1.330],p=0.043)分数和H&Y分期(β:0.098,95%CI[0.047-0.149],p<0.001)和MoCA的更快下降(β:-0.501,95%CI[-0.768至-0.234],p<0.001)和FAB评分(β:-0.358,95%CI[-0.587至-0.129],p=0.002)。较高的基线血浆GFAP预测更快速的进展为姿势不稳定(风险比:1.009,95%CI[1.001-1.017],p=0.033)。
结论:血浆GFAP可能是监测和预测PD疾病进展的潜在生物标志物。
Reactive astrogliosis has been demonstrated to have a role in Parkinson\'s disease (PD); however, astrocyte-specific plasma glial fibrillary acidic protein (GFAP)\'s correlation with PD progression remains unknown. We aimed to determine whether plasma GFAP can monitor and predict PD progression.
A total of 184 patients with PD and 95 healthy controls (HCs) were included in this prospective cohort
study and followed-up for 5 years. Plasma GFAP, amyloid-beta (Aβ), p-tau181, and neurofilament light chain (NfL) were measured at baseline and at 1- and 2-year follow-ups. Motor and non-motor symptoms, activities of daily living, global cognitive function, executive function, and disease stage were evaluated using the Unified Parkinson\'s Disease Rating Scale (UPDRS) part III, UPDRS-I, UPDRS-II, Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), and Hoehn and Yahr (H&Y) scales at each visit, respectively.
Plasma GFAP levels were higher in patients with PD (mean [SD]: 69.80 [36.18], pg/mL) compared to HCs (mean [SD]: 57.89 [23.54], pg/mL). Higher levels of GFAP were observed in female and older PD patients. The adjusted linear mixed-effects models showed that plasma GFAP levels were significantly associated with UPDRS-I scores (β: 0.006, 95% CI [0.001-0.011], p = 0.027). Higher baseline plasma GFAP correlated with faster increase in UPDRS-I (β: 0.237, 95% CI [0.055-0.419], p = 0.011) and UPDRS-III (β: 0.676, 95% CI [0.023-1.330], p = 0.043) scores and H&Y stage (β: 0.098, 95% CI [0.047-0.149], p < 0.001) and faster decrease in MoCA (β: - 0.501, 95% CI [- 0.768 to - 0.234], p < 0.001) and FAB scores (β: - 0.358, 95% CI [- 0.587 to - 0.129], p = 0.002). Higher baseline plasma GFAP predicted a more rapid progression to postural instability (hazard ratio: 1.009, 95% CI [1.001-1.017], p = 0.033).
Plasma GFAP might be a potential biomarker for monitoring and predicting disease progression in PD.