Cerebrospinal fluid GFAP is a predictive biomarker for conversion to dementia and Alzheimer's disease-associated biomarkers alterations among de novo Parkinson's disease patients: a prospective cohort study
作者全名："Liu, Tingting; Zuo, Hongzhou; Ma, Di; Song, Dan; Zhao, Yuying; Cheng, Oumei"
作者地址："[Liu, Tingting; Zuo, Hongzhou; Ma, Di; Song, Dan; Zhao, Yuying; Cheng, Oumei] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing 400016, Peoples R China"
通信作者："Cheng, OM (通讯作者)，Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing 400016, Peoples R China."
来源：JOURNAL OF NEUROINFLAMMATION
ESI学科分类：NEUROSCIENCE & BEHAVIOR
关键词：Parkinson's disease; Cerebrospinal fluid; Glial fibrillary acidic protein; Parkinson's Progression Markers Initiative; Cognition decline
摘要："BackgroundDementia is a prevalent non-motor manifestation among individuals with advanced Parkinson's disease (PD). Glial fibrillary acidic protein (GFAP) is an inflammatory marker derived from astrocytes. Research has demonstrated the potential of plasma GFAP to forecast the progression to dementia in PD patients with mild cognitive impairment (PD-MCI). However, the predictive role of cerebrospinal fluid (CSF) GFAP on future cognitive transformation and alterations in Alzheimer's disease (AD)-associated CSF biomarkers in newly diagnosed PD patients has not been investigated.Methods210 de novo PD patients from the Parkinson's Progression Markers Initiative were recruited. Cognitive progression in PD participants was evaluated using Cox regression. Cross-sectional and longitudinal associations between baseline CSF GFAP and cognitive function and AD-related CSF biomarkers were evaluated using multiple linear regression and generalized linear mixed model.ResultsAt baseline, the mean age of PD participants was 60.85 & PLUSMN; 9.78 years, including 142 patients with normal cognition (PD-NC) and 68 PD-MCI patients. The average follow-up time was 6.42 & PLUSMN; 1.69 years. A positive correlation was observed between baseline CSF GFAP and age (& beta; = 0.918, p < 0.001). There was no statistically significant difference in baseline CSF GFAP levels between PD-NC and PD-MCI groups. Higher baseline CSF GFAP predicted greater global cognitive decline over time in early PD patients (Montreal Cognitive Assessment, & beta; = - 0.013, p = 0.014). Furthermore, Cox regression showed that high baseline CSF GFAP levels were associated with a high risk of developing dementia over an 8-year period in the PD-NC group (adjusted HR = 3.070, 95% CI 1.119-8.418, p = 0.029). In addition, the baseline CSF GFAP was positively correlated with the longitudinal changes of not only CSF & alpha;-synuclein (& beta; = 0.313, p < 0.001), but also CSF biomarkers associated with AD, namely, amyloid-& beta; 42 (& beta; = 0.147, p = 0.034), total tau (& beta; = 0.337, p < 0.001) and phosphorylated tau (& beta; = 0.408, p < 0.001).ConclusionsCSF GFAP may be a valuable prognostic tool that can predict the severity and progression of cognitive deterioration, accompanied with longitudinal changes in AD-associated pathological markers in early PD."
基金机构："National Natural Science Foundation of China [81871002, 81471334, 81100981]; National Key Clinical Specialties Construction Program of China"
基金资助正文："This study was supported by Grants from the National Natural Science Foundation of China (81871002, 81471334, and 81100981) and the National Key Clinical Specialties Construction Program of China."