The Association of Enlarged Perivascular Space with Cerebrospinal Fluid GFAP in Early Parkinson's Disease

The glymphatic system and neuroinflammation have been implicated in the pathogenesis of Parkinson's disease (PD). This study aimed to investigate the relationships among enlarged perivascular spaces (EPVS) burden, cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) levels, and clinical symptoms in early PD.

A total of 114 de novo PD patients and 55 healthy controls (HCs) from the Parkinson's Progression Markers Initiative (PPMI) cohort were included. EPVS, which serve as indirect markers of glymphatic dysfunction, were assessed in two regions: the centrum semiovale (CSO) and the basal ganglia (BG). Additionally, CSF GFAP levels were utilized to assess neuroinflammation. Correlation and mediation analyses were conducted to explore the associations between glymphatic dysfunction, neuroinflammation, and clinical manifestations.

Compared with HCs, PD patients showed higher EPVS burden in both CSO and BG. Higher EPVS burden in CSO correlated with worse cognitive function and severe motor dysfunction, whereas that in BG correlated only with motor impairment. Although no statistically significant differences in CSF GFAP levels were observed between groups, higher GFAP levels were associated with worse cognitive and motor function in PD patients. Additionally, elevated GFAP levels correlated positively with EPVS burden in both CSO and BG. However, mediation analysis showed no significant indirect effects of EPVS or GFAP levels on clinical symptom severity.

EPVS burden in the CSO and BG are significantly correlated with CSF GFAP levels in PD patients, suggesting that a potential mutual interaction between these two pathological processes may collectively contribute to the pathogenesis of early PD.