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Cited by 46Parkinson's Disease Mechanisms and TreatmentsDementia and Cognitive Impairment ResearchNeurological disorders and treatments

Evaluation of plasma levels of NFL, GFAP, UCHL1 and tau as Parkinson's disease biomarkers using multiplexed single molecule counting

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Youssef, Priscilla, Hughes, Laura, Kim, Woojin S., Halliday, Glenda M., Lewis, Simon J. G., Cooper, Antony, Dzamko, Nicolas·2023·Scientific Reports
DOI 10.1038/s41598-023-32480-0PMC PMC10063670
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Abstract

Objective biomarkers for Parkinson’s Disease (PD) could aid early and specific diagnosis, effective monitoring of disease progression, and improved design and interpretation of clinical trials. Although alpha-synuclein remains a biomarker candidate of interest, the multifactorial and heterogenous nature of PD highlights the need for a PD biomarker panel. Ideal biomarker candidates include markers that are detectable in easily accessible samples, (ideally blood) and that reflect the underlying pathological process of PD. In the present study, we explored the diagnostic and prognostic PD biomarker potential of the SIMOA neurology 4-plex-A biomarker panel, which included neurofilament light (NFL), glial fibrillary acid protein (GFAP), tau and ubiquitin C-terminal hydrolase L1 (UCHL-1). We initially performed a serum vs plasma comparative study to determine the most suitable blood-based matrix for the measurement of these proteins in a multiplexed assay. The levels of NFL and GFAP in plasma and serum were highly correlated (Spearman rho-0.923, p < 0.0001 and rho = 0.825, p < 0.001 respectively). In contrast, the levels of tau were significantly higher in plasma compared to serum samples (p < 0.0001) with no correlation between sample type (Spearman p > 0.05). The neurology 4-plex-A panel, along with plasma alpha-synuclein was then assessed in a cross-sectional cohort of 29 PD patients and 30 controls. Plasma NFL levels positively correlated with both GFAP and alpha-synuclein levels (rho = 0.721, p < 0.0001 and rho = 0.390, p < 0.05 respectively). As diagnostic biomarkers, the control and PD groups did not differ in their mean NFL, GFAP, tau or UCHL-1 plasma levels (t test p > 0.05). As disease state biomarkers, motor severity (MDS-UPDRS III) correlated with increased NFL (rho = 0.646, p < 0.0001), GFAP (rho = 0.450, p < 0.05) and alpha-synuclein levels (rho = 0.406, p < 0.05), while motor stage (Hoehn and Yahr) correlated with increased NFL (rho = 0.455, p < 0.05) and GFAP (rho = 0.549, p < 0.01) but not alpha-synuclein levels (p > 0.05). In conclusion, plasma was determined to be most suitable blood-based matrix for multiplexing the neurology 4-plex-A panel. Given their correlation with motor features of PD, NFL and GFAP appear to be promising disease state biomarker candidates and further longitudinal validation of these two proteins as blood-based biomarkers for PD progression is warranted.

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Cited by

Sorted by citations

Authors
Youssef, P., Hughes, L., Kim, W. S., Halliday, G. M., Lewis, S. J. G., Cooper, A., & Dzamko, N.
Affiliations
  • The University of Sydney (AU)
  • Garvan Institute of Medical Research (AU)
Corresponding author
Dzamko, Nicolas
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2023-03-30
Volume
13
Issue
1
Pages
5217-5217
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-023-32480-0
PMC
PMC10063670
OpenAlex
W4362506627
Cited by
46
References
5
Citations by year
2026: 16 · 2025: 20 · 2024: 8 · 2023: 2
FWCI
7.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Health and Medical Research Council (1176607, 1195830)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
Keywords
Parkinson's disease, biomarkers, neurofilament light chain, glial fibrillary acidic protein, tau protein, UCHL1, alpha-synuclein, plasma biomarkers, disease progression, motor impairment severity, Hoehn and Yahr stage, early diagnosis, neuroinflammation, neurodegeneration
MeSH terms
Cross-Sectional Studies, Glial Fibrillary Acidic Protein, Humans, Parkinson Disease, Biomarkers, Ubiquitin Thiolesterase

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