Objective: To identify protein biomarkers in plasma of patients with Parkinson’s disease (PD).

Background: Inflammation plays a key role in the initiation and progression of PD. With the increasing evidence of peripheral pathology early in the course of PD there is a need to identify biomarkers in peripheral biological fluids in early stages of PD and in prodromal syndromes like isolated REM-sleep behaviour disorder (iRBD). Mass spectrometry (MS) has already successfully been applied to identify markers of neurodegeneration in Alzheimer’s disease (Heywood et al., 2015 Mol Neurodegener).

Method: In a discovery phase, unbiased nano 2D-LC-TOF MS and a systematic literature search identified a panel of protein biomarkers in PD and healthy controls (HC). For the validation phase a targeted mass spectrometry assay (nano LC-MSMS) was developed measuring 32 proteins and applied in plasma samples from baseline of newly diagnosed, unmedicated PD patients (according to UK brain bank criteria), matched HC and prodromal subjects with iRBD from the observational, single center De Novo Parkinson (DeNoPa) cohort. Deep clinical phenotyping in DeNoPa continued with longitudinal, biannual follow-up of up to 8 years. 

Results: Plasma Samples from 80 PD (48 male, 60 %, mean age 64 years) and 34 HC (19 male, 56 %, mean age 63 years) subjects were analyzed.  A total of 21 plasma proteins very significantly differently expressed between PD and HC. For further validation plasma samples from 17 iRBD patients (9 male, 53 %, mean age 67 years) were included into the analysis. 16 proteins differed between PD and iRBD, further nine markers between iRBD and HC in plasma samples. Among the proteins that were differently expressed in plasma were markers of neuroinflammation, including complement system and leucocyte function, as well as markers of Wnt/β-Catenin signaling. The plasma proteome in iRBD showed a greater overlap with PD.

Conclusion: This targeted MS analysis detected various markers distinguishing between PD and HC as well as iRBD and HC in plasma samples. Statistical analysis showed a cross validated PLS-DA classification model discriminate PD from HC with an AUC of 0.97.

References: Heywood WE, Galimberti D, Bliss E, Sirka E, Paterson RW, Magdalinou NK, et al. Identification of novel CSF biomarkers for neurodegeneration and their validation by a high-throughput multiplexed targeted proteomic assay. Mol Neurodegener. 2015;10:64.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/targeted-plasmaproteome-identifies-a-distinct-biomarker-panel-in-early-and-prodromal-parkinsons-disease/