Plasma glial fibrillary acidic protein as a biomarker of disease progression in Parkinson's disease: a prospective cohort study

Background 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.Methods 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 (A beta), 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.Results 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 (beta: 0.006, 95% CI [0.001-0.011], p = 0.027). Higher baseline plasma GFAP correlated with faster increase in UPDRS-I (beta: 0.237, 95% CI [0.055-0.419], p = 0.011) and UPDRS-III (beta: 0.676, 95% CI [0.023-1.330], p = 0.043) scores and H&Y stage (beta: 0.098, 95% CI [0.047-0.149], p < 0.001) and faster decrease in MoCA (beta: - 0.501, 95% CI [- 0.768 to - 0.234], p < 0.001) and FAB scores (beta: - 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).Conclusions Plasma GFAP might be a potential biomarker for monitoring and predicting disease progression in PD.