Cerebrospinal Fluid Levels of Autophagy-related Proteins Represent Potentially Novel Biomarkers of Early-Stage Parkinson’s Disease

Abstract

The roles of autophagy-related proteins as diagnostic or monitoring biomarkers in Parkinson’s disease (PD) have not been clearly elucidated. We recruited 32 patients with early-stage PD and 28 control subjects, and evaluated parkinsonian motor symptoms and dopamine transporter imaging data. Cerebrospinal fluid (CSF) levels of LC3B, Beclin1, and LAMP-2 were estimated using ELISAs, and CSF levels of ATG5, ATG7, and p62 were examined by immunoblotting. Additionally, we also assessed the levels of α-synuclein, total tau, and phosphorylated tau in CSF using ELISAs. Significant differences in the levels of LC3B, LAMP-2, and Beclin1 were observed between the PD and control groups. Using 29.8 pg/mL as the cut-off value for a diagnostic biomarker of PD, CSF LC3B levels exhibited high sensitivity (96.9%) and specificity (89.3%) with an area under the curve of 0.982. Furthermore, LC3B was significantly correlated with the asymmetry index in the caudate and putamen, as estimated by a semi-quantitative analysis of [18F] N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography (PET). CSF levels of LC3B represented a potential diagnostic and prognostic biomarker of early-stage PD in patients. Based on our findings, molecular biological changes in PD are associated with dysregulation of the lysosomal autophagy pathway.