Update on CSF Biomarkers in Parkinson's Disease

Progress in developing disease-modifying therapies in Parkinson's disease (PD) can only be achieved through reliable objective markers that help to identify subjects at risk. This includes an early and accurate diagnosis as well as continuous monitoring of disease progression and therapy response. Although PD diagnosis still relies mainly on clinical features, encouragingly, advances in biomarker discovery have been made. The cerebrospinal fluid (CSF) is a biofluid of particular interest to study biomarkers since it is closest to the brain structures and therefore could serve as an ideal source to reflect ongoing pathologic processes. According to the key pathophysiological mechanisms, the CSF status of alpha-synuclein species, markers of amyloid and tau pathology, neurofilament light chain, lysosomal enzymes and markers of neuroinflammation provide promising preliminary results as candidate biomarkers. Untargeted approaches in the field of metabolomics provide insights into novel and interconnected biological pathways. Markers based on genetic forms of PD can contribute to identifying subgroups suitable for gene-targeted treatment strategies that might also be transferable to sporadic PD. Further validation analyses in large PD cohort studies will identify the CSF biomarker or biomarker combinations with the best value for clinical and research purposes.

Automated summary

This paper emphasizes the importance of reliable objective markers for identifying individuals at risk of Parkinson's disease. Advances in biomarker discovery, particularly in the cerebrospinal fluid (CSF), have provided promising preliminary results. Potential biomarkers include alpha-synuclein species, markers of amyloid and tau pathology, neurofilament light chain, lysosomal enzymes, and markers of neuroinflammation. Metabolomics approaches have also offered insights into novel biological pathways. Genetic forms of PD can help identify subgroups suitable for targeted treatments. Further validation studies are needed to determine the most valuable CSF biomarkers or combinations for clinical and research purposes.