Association between the Amplification Parameters of the α-Synuclein Seed Amplification Assay and Clinical and Genetic Subtypes of Parkinson's Disease

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2024-12-18 DOI:10.1002/mds.30085

Piergiorgio Grillo MD, Luis Concha-Marambio PhD, Antonio Pisani MD, PhD, Giulietta Maria Riboldi MD, PhD, Un Jung Kang MD

{"title":"Association between the Amplification Parameters of the α-Synuclein Seed Amplification Assay and Clinical and Genetic Subtypes of Parkinson's Disease","authors":"Piergiorgio Grillo MD, Luis Concha-Marambio PhD, Antonio Pisani MD, PhD, Giulietta Maria Riboldi MD, PhD, Un Jung Kang MD","doi":"10.1002/mds.30085","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>α-Synuclein seed amplification assay on cerebrospinal fluid (CSF-αSyn-SAA) has shown high accuracy for Parkinson's disease (PD) diagnosis. The analysis of CSF-αSyn-SAA parameters may provide useful insight to dissect the heterogeneity of synucleinopathies.</p>\n </section>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>To assess differences in CSF-αSyn-SAA amplification parameters in participants with PD stratified by rapid eye movement (REM) sleep behavior disorder (RBD), dysautonomia, <i>GBA</i>, and <i>LRRK2</i> variants.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Clinical and CSF-αSyn-SAA data from the Parkinson's Progression Marker Initiative dataset were used. CSF-αSyn-SAA parameters included maximum fluorescence (F<sub>max</sub>), time to reach 50% of F<sub>max</sub> (T50), time to threshold (TTT), slope, and area under the curve (AUC). Sporadic PD (n = 371) was stratified according to RBD and dysautonomia (DysA) symptoms. Genetic PD included carriers of pathogenic variants of <i>GBA</i> (<i>GBA</i>-PD, n = 52) and <i>LRRK2</i> (<i>LRRK2</i>-PD, n = 124) gene.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>CSF-αSyn-SAA was positive in 77% of <i>LRRK2</i>-PD, 92.3% of <i>GBA</i>-PD, and 93.8% of sporadic PD. The <i>LRRK2</i>-PD cohort showed longer T50 and TTT, and smaller AUC than <i>GBA</i>-PD (<i>P</i> = 0.029, <i>P</i> = 0.029, <i>P</i> = 0.016, respectively) and sporadic PD (<i>P</i> = 0.034, <i>P</i> = 0.033, <i>P</i> = 0.014, respectively). In the sporadic cohort, CSF-αSyn-SAA parameters were similar between PD with (n = 157) and without (n = 190) RBD, whereas participants with DysA (n = 193) presented shorter T50 (<i>P</i> = 0.026) and larger AUC (<i>P</i> = 0.029) than those without (n = 150).</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>CSF-αSyn-SAA parameters vary across genetic and non-genetic PD subtypes at the group level. These differences are mostly driven by the presence of <i>LRRK2</i> variants and DysA. Significant overlaps in the amplification parameter values exist between groups and limit their use at the individual level. Further studies are necessary to understand the mechanisms of CSF-αSyn-SAA parameter differences. © 2024 International Parkinson and Movement Disorder Society.</p>\n </section>\n </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 2","pages":"305-314"},"PeriodicalIF":7.4000,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Movement Disorders","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/mds.30085","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

α-Synuclein seed amplification assay on cerebrospinal fluid (CSF-αSyn-SAA) has shown high accuracy for Parkinson's disease (PD) diagnosis. The analysis of CSF-αSyn-SAA parameters may provide useful insight to dissect the heterogeneity of synucleinopathies.

Objective

To assess differences in CSF-αSyn-SAA amplification parameters in participants with PD stratified by rapid eye movement (REM) sleep behavior disorder (RBD), dysautonomia, GBA, and LRRK2 variants.

Methods

Clinical and CSF-αSyn-SAA data from the Parkinson's Progression Marker Initiative dataset were used. CSF-αSyn-SAA parameters included maximum fluorescence (F_max), time to reach 50% of F_max (T50), time to threshold (TTT), slope, and area under the curve (AUC). Sporadic PD (n = 371) was stratified according to RBD and dysautonomia (DysA) symptoms. Genetic PD included carriers of pathogenic variants of GBA (GBA-PD, n = 52) and LRRK2 (LRRK2-PD, n = 124) gene.

Results

CSF-αSyn-SAA was positive in 77% of LRRK2-PD, 92.3% of GBA-PD, and 93.8% of sporadic PD. The LRRK2-PD cohort showed longer T50 and TTT, and smaller AUC than GBA-PD (P = 0.029, P = 0.029, P = 0.016, respectively) and sporadic PD (P = 0.034, P = 0.033, P = 0.014, respectively). In the sporadic cohort, CSF-αSyn-SAA parameters were similar between PD with (n = 157) and without (n = 190) RBD, whereas participants with DysA (n = 193) presented shorter T50 (P = 0.026) and larger AUC (P = 0.029) than those without (n = 150).

Conclusion

CSF-αSyn-SAA parameters vary across genetic and non-genetic PD subtypes at the group level. These differences are mostly driven by the presence of LRRK2 variants and DysA. Significant overlaps in the amplification parameter values exist between groups and limit their use at the individual level. Further studies are necessary to understand the mechanisms of CSF-αSyn-SAA parameter differences. © 2024 International Parkinson and Movement Disorder Society.

查看原文本刊更多论文

α-突触核蛋白种子扩增试验的扩增参数与帕金森病临床和遗传亚型的关系

背景：脑脊液α-突触核蛋白种子扩增试验（CSF-αSyn-SAA）对帕金森病（PD）的诊断具有较高的准确性。CSF-αSyn-SAA参数的分析可能为解剖突触核蛋白病的异质性提供有用的见解。目的：评估快速眼动（REM）睡眠行为障碍（RBD）、自主神经异常、GBA和LRRK2变异PD患者CSF-αSyn-SAA扩增参数的差异。方法：采用帕金森病进展标志物倡议数据集的临床和CSF-αSyn-SAA数据。CSF-αSyn-SAA参数包括最大荧光（Fmax）、到达Fmax 50%的时间（T50）、到达阈值时间（TTT）、斜率和曲线下面积（AUC）。根据RBD和自主神经异常（DysA）症状对散发性PD （n = 371）进行分层。遗传性PD包括GBA （GBA-PD, n = 52）和LRRK2 （LRRK2-PD, n = 124）基因致病变异携带者。结果：CSF-αSyn-SAA在LRRK2-PD中阳性77%，在GBA-PD中阳性92.3%，在散发性PD中阳性93.8%。LRRK2-PD组T50和TTT较GBA-PD组（P = 0.029, P = 0.029, P = 0.016）和散发性PD组（P = 0.034, P = 0.033, P = 0.014）更长，AUC较小。在散发性队列中，PD伴RBD （n = 157）和不伴RBD （n = 190）患者的CSF-αSyn-SAA参数相似，而DysA伴RBD （n = 193）患者的T50 （P = 0.026）和AUC （P = 0.029）较不伴RBD （n = 150）的患者短。结论：脑脊液-αSyn-SAA参数在遗传和非遗传PD亚型组水平上存在差异。这些差异主要是由LRRK2变体和DysA的存在驱动的。在群体之间存在显著的放大参数值重叠，限制了它们在个体水平上的使用。脑脊液-αSyn-SAA参数差异的机制有待进一步研究。©2024国际帕金森和运动障碍学会。

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

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.