Objective: To identify the ability of a panel of plasma biomarkers to predict disease progression in PD patients

Background: Plasma neurofilament light chain (NfL) has been identified as one of the most promising biomarkers for predicting disease progression in several conditions, including Parkinson’s disease (PD) (Pilotto et al. 2021, Ashton et al. 2021).  Recent studies reported the utility of plasma phospho-tau, beta-amyloid and glial fibrillary acid protein (GFAP) for diagnostic and prognostic purposes of Alzheimer’s disease and other neurodegenerative conditions (Chatterjee et al. 2021). In this study, we evaluated the ability of a panel of plasma biomarkers to predict disease progression in PD patients.

Method: We measured plasma p-tau181, p-tau231, Aβ40, Aβ42, GFAP and NfL using Single molecule array (Simoa) assays in healthy controls (HC) and consecutive PD patients who underwent an extensive motor and non-motor assessment at baseline and two to five years of follow-up. Differences in biomarkers level between PD and HC were evaluated adjusting for the effect of age and sex. In PD patients, the correlation between plasma biomarkers and motor scores at baseline and at follow-up were evaluated using partial correlation analyses. We also performed linear regression and Cox regression analyses on disability milestones to evaluate the best combination of plasma predictors of progression in the sample.

Results: One hundred ninety PD and 106 HC entered the analyses. PD patients exhibited higher p-tau181, p-tau231 and lower Aβ42 compared with HC but similar NfL, GFAP and Aβ40 levels. All biomarkers correlated with age and disease duration, whereas NfL, GFAP and ptau181 additionally correlated with baseline motor severity. At follow-up, NfL emerged as best predictor of motor progression assessed by changes in MDS-UPDRS (linear regression analyses) and gait dependency (COX regression) adjusting for the effect of age, sex, disease duration, baseline motor/non-motor variables.

Conclusion: The present findings confirm plasma NfL as the best predictor of motor progression in PD in comparison with other plasma biomarkers. Larger on-going studies with longitudinal plasma assessment are needed to evaluate the potential value of other biomarkers for tracking disease progression or presence of co-pathologies over time.

References: Ashton NJ, Janelidze S, Al Khleifat A, Leuzy A, van der Ende EL, Karikari TK, Benedet AL, Pascoal TA, Lleó A, Parnetti L, Galimberti D, Bonanni L, Pilotto A, Padovani A, Lycke J, Novakova L, Axelsson M, Velayudhan L, Rabinovici GD, Miller B, Pariante C, Nikkheslat N, Resnick SM, Thambisetty M, Schöll M, Fernández-Eulate G, Gil-Bea FJ, López de Munain A, Al-Chalabi A, Rosa-Neto P, Strydom A, Svenningsson P, Stomrud E, Santillo A, Aarsland D, van Swieten JC, Palmqvist S, Zetterberg H, Blennow K, Hye A, Hansson O. A multicentre validation study of the diagnostic value of plasma neurofilament light. Nat Commun. 2021 Jun 7;12(1):3400. doi: 10.1038/s41467-021-23620-z.

Chatterjee P, Pedrini S, Ashton NJ, Tegg M, Goozee K, Singh AK, Karikari TK, Simrén J, Vanmechelen E, Armstrong NJ, Hone E, Asih PR, Taddei K, Doré V, Villemagne VL, Sohrabi HR, Zetterberg H, Masters CL, Blennow K, Martins RN. Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer’s disease. Alzheimers Dement. 2021 Sep 8. doi:

Pilotto A, Imarisio A, Conforti F, Scalvini A, Masciocchi S, Nocivelli S, Turrone R, Gipponi S, Cottini E, Borroni B, Rizzetti MC, Pizzi M, Bonanni L, Sturchio A, Espay AJ, Zetterberg H, Ashton NJ, Hye A, Padovani A. Plasma NfL, clinical subtypes and motor progression in Parkinson’s disease.
Parkinsonism Relat Disord. 2021 Jun;87:41-47. doi: 10.1016/j.parkreldis.2021.04.016.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/plasma-biomarkers-of-disease-progression-in-parkinsons-disease/