Identification of candidate cerebrospinal fluid biomarkers in parkinsonism using quantitative proteomics

Good work by Nadia... it was a huge amount of work to gather samples from so many patients... but of course this is really important. You need large numbers to capture the heterogeneity in the diseases. It's been said many times but biomarkers for all of these diseases are desperately needed. This work is definitely a positive step in that direction...

Parkinsonism Relat Disord. 2017 Jan 31. pii: S1353-8020(17)30030-5. doi: 10.1016/j.parkreldis.2017.01.016. [Epub ahead of print]
Magdalinou NK, Noyce AJ, Pinto R, Lindstrom E, Holmén-Larsson J, Holtta M, Blennow K, Morris HR, Skillbäck T, Warner TT, Lees AJ, Pike I, Ward M, Zetterberg H, Gobom J.

http://www.prd-journal.com/article/S1353-8020(17)30030-5/abstract

INTRODUCTION: Neurodegenerative parkinsonian syndromes have significant clinical and pathological overlap, making early diagnosis difficult. Cerebrospinal fluid (CSF) biomarkers may aid the differentiation of these disorders, but other than α-synuclein and neurofilament light chain protein, which have limited diagnostic power, specific protein biomarkers remain elusive.

OBJECTIVES: To study disease mechanisms and identify possible CSF diagnostic biomarkers through discovery proteomics, which discriminate parkinsonian syndromes from healthy controls.

METHODS: CSF was collected consecutively from 134 participants; Parkinson's disease (n = 26), atypical parkinsonian syndromes (n = 78, including progressive supranuclear palsy (n = 36), multiple system atrophy (n = 28), corticobasal syndrome (n = 14)), and elderly healthy controls (n = 30). Participants were divided into a discovery and a validation set for analysis. The samples were subjected to tryptic digestion, followed by liquid chromatography-mass spectrometry analysis for identification and relative quantification by isobaric labelling. Candidate protein biomarkers were identified based on the relative abundances of the identified tryptic peptides. Their predictive performance was evaluated by analysis of the validation set.

RESULTS: 79 tryptic peptides, derived from 26 proteins were found to differ significantly between atypical parkinsonism patients and controls. They included acute phase/inflammatory markers and neuronal/synaptic markers, which were respectively increased or decreased in atypical parkinsonism, while their levels in PD subjects were intermediate between controls and atypical parkinsonism.

CONCLUSION: Using an unbiased proteomic approach, proteins were identified that were able to differentiate atypical parkinsonian syndrome patients from healthy controls. Our study indicates that markers that may reflect neuronal function and/or plasticity, such as the amyloid precursor protein, and inflammatory markers may hold future promise as candidate biomarkers in parkinsonism.