Plasma GFAP and NfL associate with cerebral glucose metabolism in putative brain-first and body-first Parkinson’s disease subtypes

The recently proposed body-first and brain-first subtypes are classified based on the initial localization of α-synuclein inclusions. This study investigated plasma biomarkers and cerebral glucose metabolism characteristics in putative brain-first and body-first subtypes in PD subjects. PD patients without possible RBD (PD^pRBD-) (n = 58) and with possible RBD symptoms discovered before motor symptoms (PD^pRBD+) (n = 43) were recruited. Single-molecule array (SimoA) was used for measuring plasma biomarkers, including glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), Tau and phosphorylated-tau 181 (pTau-181). All participants underwent ¹⁸F-fluorodeoxyglucose (FDG) PET scans. Compared to PD^pRBD- patients, PD^pRBD+ patients exhibited significantly increased plasma GFAP levels and reduced ¹⁸F-FDG uptake in cortical regions. Notably, plasma GFAP and NfL levels correlated with cerebral glucose metabolism in PD^pRBD- patients. Our study identified the association between plasma GFAP and NfL levels and cerebral glucose metabolism in PD^pRBD- patients. Further large-scale longitudinal studies are required.