Liu Yumei, Wang Jing, Ning Fangbo, Wang Guojun, Xie Anmu
Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Neurology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, China.
Clin Transl Sci. 2024 Dec;17(12):e70111. doi: 10.1111/cts.70111.
Glial fibrillary acidic protein (GFAP) is an intermediate filament protein expressed mainly in astrocytes of the central nervous system (CNS), a potential biomarker of cognitive decline in Parkinson's disease (PD). The central motor subtypes of PD include tremor-dominant (TD), postural instability and gait disorder (PIGD), and indeterminate subtypes, whose different course of disease requires the development of biomarkers that can predict progression based on motor subtypes. In this study, we aimed to assess the predictive value of cerebrospinal fluid (CSF) GFAP for PD motor subtypes in PD. Two hundred and sixteen PD patients were recruited in our study from the progression markers initiative. Patients were subgrouped into TD, PIGD, and indeterminate subtypes. Longitudinal relationships between baseline CSF GFAP and cognitive function and CSF biomarkers were assessed using linear mixed-effects models. Cox regression was used to detect cognitive progression in TD patients. The baseline and longitudinal increases in CSF GFAP were associated with a greater decline in episodic memory, CSF α-syn, and a greater increase of CSF NfL in TD and TD-male subtypes. Cox regression showed that higher baseline CSF GFAP levels were corrected with a higher risk of developing mild cognitive impairment (MCI) over a 4-year period in the PD with normal cognition (NC) group (adjusted HR = 1.607, 95% CI 1.907-2.354, p = 0.01). CSF GFAP might be a promising predictor of cognition decline in TD.
胶质纤维酸性蛋白（GFAP）是一种主要在中枢神经系统（CNS）的星形胶质细胞中表达的中间丝蛋白，是帕金森病（PD）认知功能下降的潜在生物标志物。PD的中枢运动亚型包括震颤为主型（TD）、姿势不稳和步态障碍型（PIGD）以及不确定型，其不同的疾病进程需要开发能够根据运动亚型预测疾病进展的生物标志物。在本研究中，我们旨在评估脑脊液（CSF）GFAP对PD患者运动亚型的预测价值。我们从疾病进展标志物研究中招募了216例PD患者。患者被分为TD、PIGD和不确定型。使用线性混合效应模型评估基线CSF GFAP与认知功能和CSF生物标志物之间的纵向关系。Cox回归用于检测TD患者的认知进展。CSF GFAP的基线水平和纵向升高与TD和TD男性亚型的情景记忆、CSFα-突触核蛋白的更大下降以及CSF神经丝轻链（NfL）的更大升高相关。Cox回归显示，在认知正常（NC）的PD组中，较高的基线CSF GFAP水平与4年内发生轻度认知障碍（MCI）的较高风险相关（调整后的HR = 1.607，95%CI 1.907 - 2.354，p = 0.01）。CSF GFAP可能是TD患者认知功能下降的一个有前景的预测指标。
