Integration of TSPO PET and fluid biomarkers to assess neuroinflammation in Parkinson's disease.

Abstract

Microglia-mediated neuroinflammation is implicated in Parkinson's disease (PD), but its relationship with clinical severity remains controversial. Using [¹⁸F]FEPPA translocator protein (TSPO) PET with plasma biomarkers, we examined associations among neuroinflammation, glial activation, neuronal injury, and motor and cognitive impairment. Ninety participants (71 patients with PD and 19 age-matched controls) underwent TSPO PET and plasma measurements of soluble triggering receptor expression on myeloid cells-2 (sTREM2), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Binding potential relative to the non-displaceable compartment (BP_ND) was quantified across cortical and subcortical regions. Motor severity was assessed with Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III and Hoehn-Yahr stage in the off state. Cognitive performance was evaluated using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). PD dementia (PDD) was diagnosed according to MDS Task Force criteria. Patients with PD had higher TSPO BP_ND in the basal ganglia than controls (p = 0.01), most prominent in advanced motor stage (Hoehn-Yahr ≥ 3) and PDD, particularly in the pallidum (p < 0.01). Higher MDS-UPDRS part III scores correlated with increased BP_ND in the bilateral putamen and frontal and parietal cortices. Patients with PDD had significantly higher pallidal BP_ND than those without cognitive impairment and controls (both p < 0.001). Higher pallidal BP_ND was associated with worse global cognitive performance (MMSE, MoCA) and correlated with plasma NfL, GFAP, and sTREM2 levels, especially in patients with advanced disease. TSPO PET with plasma biomarkers revealed region-specific neuroinflammation associated with motor and cognitive severity in Parkinson's disease progression.