Longitudinal correlation of cerebrospinal fluid GFAP and the progression of cognition decline in different clinical subtypes of Parkinson's disease

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.