Biomarkers of cerebral glucose metabolism and neurodegeneration in Parkinson's disease: a cerebrospinal fluid-based study

Background: Several biomarkers have been evaluated in Parkinson's disease (PD); cerebrospinal fluid (CSF) levels of lactate may reflect cerebral metabolism function and CSF amyloid-β42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau) concentrations may detect an underlying neurodegenerative process. Objective: CSF levels of lactate, Aβ 42, t-tau, and p-tau were measured in patients with mild to moderate PD. It also assessed CSF levels of dopamine (DA) and its metabolite 3,4-Dihydroxyphenylacetic acid (DOPAC), exploring their relations with the other CSF biomarkers. Methods: 101 drug-naive PD patients and 60 controls were included. Participants underwent clinical assessments and CSF biomarker analysis. Patients were divided into subgroups according to their H&Y stage (PD-1, PD-2, PD-3). Results: PD patients showed higher lactate levels (M = 1.91; p = 0.03) and lower Aβ 42 (M = 595; p <  0.001) and DA levels (M = 0.32; p = 0.04) than controls (Mlactate = 1.72; MAβ42 = 837; MDA = 0.50), while no significant differences were found in t-tau, p-tau and DOPAC concentrations. Considering the subgroup analysis, PD-3 group had higher lactate (M = 2.12) and t-tau levels (M = 333) than both PD-1 (Mlactate = 1.75, p = 0.006; Mt - tau = 176, p = 0.008) and PD-2 groups (Mlactate = 1.91, p = 0.01; Mt - tau = 176, p = 0.03), as well as the controls (Mlactate = 1.72, p = 0.04; Mt - tau = 205, p = 0.04). PD-2 group showed higher lactate levels than PD-1 group (p = 0.04) and controls (p = 0.03). Conclusion: This CSF-based study shows that lactate levels in PD correlated with both clinical disease progression and neurodegeneration biomarkers, such as tau proteins and DA. Further studies should explore the clinical potential of measuring CSF biomarkers for better understanding the role of brain energy metabolism in PD, for research and therapeutic options.