Cerebrospinal Fluid Biomarkers for Diagnosis of Parkinson's disease: A Systematic Review.

Parkinson's disease (PD) is a neurodegenerative disorder that presents challenges in early diagnosis, particularly in its prodromal stages. PD is characterized by motor and non-motor symptoms, and it remains challenging to diagnose in its early stages. The use of cerebrospinal fluid (CSF) biomarkers has shown promise as an adjunctive tool for early detection and monitoring of disease progression. The aim of this systematic review was to evaluate the diagnostic potential of CSF biomarkers in PD. We focused on assessing the reliability, sensitivity, specificity, and utility of various CSF biomarkers for the early and accurate diagnosis of PD. A comprehensive search was conducted across multiple databases, including PubMed, Scopus, and Web of Science, to identify relevant studies published from January 2015 to November 2024. Studies were included if they examined CSF biomarkers in human PD patients, and compared to healthy controls or other neurodegenerative diseases. Data on sample size, biomarker types, and diagnostic accuracy were extracted from 34 eligible studies. The methodological quality of the studies was assessed using standard tools, and a qualitative synthesis was performed using PRISMA tools. Analysis was done to assess the diagnostic performance of selected biomarkers. The review identified several promising CSF biomarkers, including α-synuclein, neurofilament light chain (NfL), DJ-1, tau, and exosomal biomarkers. Of these, α-synuclein demonstrated the highest diagnostic accuracy with a sensitivity of 70-85% and specificity of 75-90%. NfL also showed a strong sensitivity (65-85%) for detecting neuronal injury, while DJ-1 exhibited a high specificity for early-stage PD. Multi-biomarker panels, including combinations of α-synuclein, tau, and NfL, demonstrated superior diagnostic accuracy compared to individual biomarkers. The variability in the biomarkers' performance was noted across studies, indicating the need for standardization in biomarker assays and further validation through larger, multicenter studies. CSF biomarkers hold significant promise for improving the diagnosis of PD, particularly when used in combination. However, more research is needed to establish standardized protocols and evaluate their role in clinical practice. Multi-biomarker panels show potential as a diagnostic tool, but further investigation is required to confirm their clinical utility and cost-effectiveness in diverse populations. Future studies should focus on the longitudinal tracking of these biomarkers for monitoring disease progression and therapeutic response.