Objective: The aim of this study was to identify cerebrospinal fluid peptides that are differential in the cerebrospinal fluid of patients with Parkinson´s disease. Those peptides might be used as biomarkers or provide insight into the pathophysiology of Parkinson´s disease.

Background: Due to the fact, that the symptomatology is very similar between Parkinson’s disease and other neurological disorders, diagnosis can be challenging. This is especially the case in early disease states, where many symptoms are mild or not yet developed. In clinical routine biomarkers would help to overcome this challenge and to therewith ensure diagnosis, moreover they could help to monitor disease progression as well as therapeutic intervention. For identification of Parkinson’s disease specific biomarkers, we focused on proteins in cerebrospinal fluid.

Method: Cerebrospinal fluid samples of patients with Parkinson’s disease and controls were characterized by clinical parameters and then matched accordingly. Cerebrospinal fluid proteins were denaturized, acetylated, and proteolytic digested by trypsin into peptides. The complex peptide samples were spiked with indexed retention time peptides and measured using HPLC-MS/MS. The mass spectrometer operated in data independent acquisition mode. Finally, the data were analyzed using bioinformatics and statistics, including spectral libraries (Schilde et al. 2020).

Results: The study group consisted of 124 subjects. Of those, 63  had Parkinson´s disease, and 61 were controls. 31.8 % of patients with Parkinson´s disease and 44 % of controls were women. The mean age of subjects with Parkinson´s disease was 68 years (SD: 10.4 years) and for controls 66 years (SD: 12.7 years). Furthermore, the subjects with Parkinson´s disease represent the population of those with Parkinson´s disease in terms of clinical factors, like Hoehn and Yahr Score and the incidence of tremor. Using various strict filter criteria, including p-value and fold change, 12 peptides belonging to 8 proteins were identified as either up- or downregulated in the CSF of patients with Parkinson´s disease.

Conclusion: The identified peptides might be useful biomarker candidates. Yet, there is further need for validation in different subject populations and using different methods. Those are currently in work (Gomes et al. 2021).

References: Schilde, L. M., S. Steinbach, B. Serschnitzki, F. Maass, M. Bähr, P. Lingor, K. Marcus & C. May (2020) Human cerebrospinal fluid data for use as spectral library, for biomarker research. Data Brief, 32, 106048. L. C. Gomes, A. Roser, G. Jain, T. Pena-Centeno, F. Maass, L. Schilde, M. Bähr, K. Marcus, A. Fischer, P. Lingor (2021) MicroRNAs from extracellular vesicles as a signature for Parkinson’s disease. Clinical and Translational Medicine. DOI: 10.1002/ctm2.357 Accepted.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/biomarker-candidates-peptides-identified-to-be-differentially-abundant-in-cerebrospinal-fluid-of-patients-with-parkinsons-disease/