Phosphorylated α-synuclein in CSF and plasma does not reflect synucleinopathy
Abstract We developed a highly sensitive and specific single-molecule array (Simoa) Homebrew assay for quantification of phosphorylated α-synuclein at serine 129 (pS129 α-syn) and evaluated its performance in human cerebrospinal fluid (CSF) and plasma. Using a cohort of patients with Parkinson’s dis...
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Nature Portfolio
2025-08-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-025-01086-w |
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| author | Giovanni Bellomo Erik Stoops Jeroen Vanbrabant Leentje Demeyer Cindy Francois Melanie Vanhooren Yihua Ma Carly M. Farris Luis Concha-Marambio Federico Paolini Paoletti Lorenzo Gaetani Lucilla Parnetti Davide Chiasserini |
| author_facet | Giovanni Bellomo Erik Stoops Jeroen Vanbrabant Leentje Demeyer Cindy Francois Melanie Vanhooren Yihua Ma Carly M. Farris Luis Concha-Marambio Federico Paolini Paoletti Lorenzo Gaetani Lucilla Parnetti Davide Chiasserini |
| author_sort | Giovanni Bellomo |
| collection | DOAJ |
| description | Abstract We developed a highly sensitive and specific single-molecule array (Simoa) Homebrew assay for quantification of phosphorylated α-synuclein at serine 129 (pS129 α-syn) and evaluated its performance in human cerebrospinal fluid (CSF) and plasma. Using a cohort of patients with Parkinson’s disease (PD), Alzheimer’s disease (AD), and neurological controls with available CSF α-synuclein seed amplification assay (synSAA) outcome, we examined pS129 α-syn alongside N-terminal and C-terminal α-syn proteoforms. Our results showed that pS129 α-syn concentration was about 1% and 0.001% of the other α-syn species in CSF and plasma, respectively. We found no correlation between pS129 α-syn and synSAA outcome, indicating that soluble pS129 α-syn in CSF and plasma does not reflect presence of synucleinopathy. Interestingly, pS129 α-syn and other α-syn forms were significantly increased in AD compared to PD and controls, supporting the role of α-syn as biomarker of synaptic degeneration in AD. |
| format | Article |
| id | doaj-art-ac5ffc246c78465f99c59e1febbf4994 |
| institution | Kabale University |
| issn | 2373-8057 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-ac5ffc246c78465f99c59e1febbf49942025-08-20T04:01:56ZengNature Portfolionpj Parkinson's Disease2373-80572025-08-011111910.1038/s41531-025-01086-wPhosphorylated α-synuclein in CSF and plasma does not reflect synucleinopathyGiovanni Bellomo0Erik Stoops1Jeroen Vanbrabant2Leentje Demeyer3Cindy Francois4Melanie Vanhooren5Yihua Ma6Carly M. Farris7Luis Concha-Marambio8Federico Paolini Paoletti9Lorenzo Gaetani10Lucilla Parnetti11Davide Chiasserini12Laboratory of Clinical Neurochemistry, Section of Neurology, Department of Medicine and Surgery, University of PerugiaADx NeuroSciencesADx NeuroSciencesADx NeuroSciencesADx NeuroSciencesADx NeuroSciencesR&D unit, Amprion Inc, San DiegoR&D unit, Amprion Inc, San DiegoR&D unit, Amprion Inc, San DiegoCentro Disturbi della Memoria, Clinica Neurologica, Azienda Ospedaliera di PerugiaLaboratory of Clinical Neurochemistry, Section of Neurology, Department of Medicine and Surgery, University of PerugiaLaboratory of Clinical Neurochemistry, Section of Neurology, Department of Medicine and Surgery, University of PerugiaSection of Physiology and Biochemistry, Department of Medicine and Surgery, University of PerugiaAbstract We developed a highly sensitive and specific single-molecule array (Simoa) Homebrew assay for quantification of phosphorylated α-synuclein at serine 129 (pS129 α-syn) and evaluated its performance in human cerebrospinal fluid (CSF) and plasma. Using a cohort of patients with Parkinson’s disease (PD), Alzheimer’s disease (AD), and neurological controls with available CSF α-synuclein seed amplification assay (synSAA) outcome, we examined pS129 α-syn alongside N-terminal and C-terminal α-syn proteoforms. Our results showed that pS129 α-syn concentration was about 1% and 0.001% of the other α-syn species in CSF and plasma, respectively. We found no correlation between pS129 α-syn and synSAA outcome, indicating that soluble pS129 α-syn in CSF and plasma does not reflect presence of synucleinopathy. Interestingly, pS129 α-syn and other α-syn forms were significantly increased in AD compared to PD and controls, supporting the role of α-syn as biomarker of synaptic degeneration in AD.https://doi.org/10.1038/s41531-025-01086-w |
| spellingShingle | Giovanni Bellomo Erik Stoops Jeroen Vanbrabant Leentje Demeyer Cindy Francois Melanie Vanhooren Yihua Ma Carly M. Farris Luis Concha-Marambio Federico Paolini Paoletti Lorenzo Gaetani Lucilla Parnetti Davide Chiasserini Phosphorylated α-synuclein in CSF and plasma does not reflect synucleinopathy npj Parkinson's Disease |
| title | Phosphorylated α-synuclein in CSF and plasma does not reflect synucleinopathy |
| title_full | Phosphorylated α-synuclein in CSF and plasma does not reflect synucleinopathy |
| title_fullStr | Phosphorylated α-synuclein in CSF and plasma does not reflect synucleinopathy |
| title_full_unstemmed | Phosphorylated α-synuclein in CSF and plasma does not reflect synucleinopathy |
| title_short | Phosphorylated α-synuclein in CSF and plasma does not reflect synucleinopathy |
| title_sort | phosphorylated α synuclein in csf and plasma does not reflect synucleinopathy |
| url | https://doi.org/10.1038/s41531-025-01086-w |
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