Evaluation of plasma levels of NFL, GFAP, UCHL1 and tau as Parkinson's disease biomarkers using multiplexed single molecule counting
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 hetero...
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| Format: | Article |
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Nature Portfolio
2023-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-32480-0 |
| _version_ | 1797853836142968832 |
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| author | Priscilla Youssef Laura Hughes Woojin S. Kim Glenda M. Halliday Simon J. G. Lewis Antony Cooper Nicolas Dzamko |
| author_facet | Priscilla Youssef Laura Hughes Woojin S. Kim Glenda M. Halliday Simon J. G. Lewis Antony Cooper Nicolas Dzamko |
| author_sort | Priscilla Youssef |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T19:57:13Z |
| format | Article |
| id | doaj.art-1fb73d2a0cf2476ba2fe850027c13533 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T19:57:13Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-1fb73d2a0cf2476ba2fe850027c135332023-04-03T05:24:42ZengNature PortfolioScientific Reports2045-23222023-03-0113111110.1038/s41598-023-32480-0Evaluation of plasma levels of NFL, GFAP, UCHL1 and tau as Parkinson's disease biomarkers using multiplexed single molecule countingPriscilla Youssef0Laura Hughes1Woojin S. Kim2Glenda M. Halliday3Simon J. G. Lewis4Antony Cooper5Nicolas Dzamko6Faculty of Medicine and Health and the Brain and Mind Centre, School of Medical Sciences, University of SydneyFaculty of Medicine and Health and the Brain and Mind Centre, School of Medical Sciences, University of SydneyFaculty of Medicine and Health and the Brain and Mind Centre, School of Medical Sciences, University of SydneyFaculty of Medicine and Health and the Brain and Mind Centre, School of Medical Sciences, University of SydneyFaculty of Medicine and Health and the Brain and Mind Centre, School of Medical Sciences, University of SydneyGarvan Institute of Medical ResearchFaculty of Medicine and Health and the Brain and Mind Centre, School of Medical Sciences, University of SydneyAbstract 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.https://doi.org/10.1038/s41598-023-32480-0 |
| spellingShingle | Priscilla Youssef Laura Hughes Woojin S. Kim Glenda M. Halliday Simon J. G. Lewis Antony Cooper Nicolas Dzamko Evaluation of plasma levels of NFL, GFAP, UCHL1 and tau as Parkinson's disease biomarkers using multiplexed single molecule counting Scientific Reports |
| title | Evaluation of plasma levels of NFL, GFAP, UCHL1 and tau as Parkinson's disease biomarkers using multiplexed single molecule counting |
| title_full | Evaluation of plasma levels of NFL, GFAP, UCHL1 and tau as Parkinson's disease biomarkers using multiplexed single molecule counting |
| title_fullStr | Evaluation of plasma levels of NFL, GFAP, UCHL1 and tau as Parkinson's disease biomarkers using multiplexed single molecule counting |
| title_full_unstemmed | Evaluation of plasma levels of NFL, GFAP, UCHL1 and tau as Parkinson's disease biomarkers using multiplexed single molecule counting |
| title_short | Evaluation of plasma levels of NFL, GFAP, UCHL1 and tau as Parkinson's disease biomarkers using multiplexed single molecule counting |
| title_sort | evaluation of plasma levels of nfl gfap uchl1 and tau as parkinson s disease biomarkers using multiplexed single molecule counting |
| url | https://doi.org/10.1038/s41598-023-32480-0 |
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