Phosphorylated α-synuclein in CSF and plasma does not reflect synucleinopathy

IF 8.2 1区医学 Q1 NEUROSCIENCES

NPJ Parkinson's Disease Pub Date : 2025-08-07 DOI:10.1038/s41531-025-01086-w

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

{"title":"Phosphorylated α-synuclein in CSF and plasma does not reflect synucleinopathy","authors":"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","doi":"10.1038/s41531-025-01086-w","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"1 1","pages":""},"PeriodicalIF":8.2000,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"NPJ Parkinson's Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41531-025-01086-w","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

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.

Abstract Image

查看原文本刊更多论文

脑脊液和血浆α-突触核蛋白磷酸化不反映突触核蛋白病

我们建立了一种高灵敏度和特异性的单分子阵列（Simoa）自制检测方法，用于定量丝氨酸129磷酸化α-突触核蛋白（pS129 α-syn），并评估其在人脑脊液（CSF）和血浆中的性能。利用一组帕金森病（PD）、阿尔茨海默病（AD）患者和具有脑脊液α-突触核蛋白种子扩增试验（synSAA）结果的神经系统对照患者，我们检测了pS129 α-syn与n端和c端α-syn蛋白形态。结果表明，pS129 α-syn在脑脊液和血浆中的浓度分别约为其他α-syn的1%和0.001%。我们发现pS129 α-syn与synSAA结果没有相关性，表明CSF和血浆中可溶性pS129 α-syn并不反映突触核蛋白病的存在。有趣的是，与PD和对照组相比，pS129 α-syn和其他α-syn形式在AD中显著增加，支持α-syn作为AD中突触变性的生物标志物的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

NPJ Parkinson's Disease Medicine-Neurology (clinical)

CiteScore

9.80

自引率

5.70%

发文量

156

审稿时长

11 weeks

期刊介绍： npj Parkinson's Disease is a comprehensive open access journal that covers a wide range of research areas related to Parkinson's disease. It publishes original studies in basic science, translational research, and clinical investigations. The journal is dedicated to advancing our understanding of Parkinson's disease by exploring various aspects such as anatomy, etiology, genetics, cellular and molecular physiology, neurophysiology, epidemiology, and therapeutic development. By providing free and immediate access to the scientific and Parkinson's disease community, npj Parkinson's Disease promotes collaboration and knowledge sharing among researchers and healthcare professionals.