α-突触核蛋白种子扩增试验的扩增参数与帕金森病临床及基因亚型之间的关联

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

作者信息

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

机构信息

The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology, NYU Langone Health, New York City, New York, USA.

Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.

出版信息

Mov Disord. 2025 Feb;40(2):305-314. doi: 10.1002/mds.30085. Epub 2024 Dec 18.

DOI:10.1002/mds.30085

PMID:39692283

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11904876/

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), time to reach 50% of F (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.

摘要

背景

脑脊液α-突触核蛋白种子扩增检测（CSF-αSyn-SAA）对帕金森病（PD）诊断具有较高的准确性。分析CSF-αSyn-SAA参数可能有助于剖析突触核蛋白病的异质性。

目的

评估快速眼动（REM）睡眠行为障碍（RBD）、自主神经功能障碍、GBA和LRRK2基因变异分层的PD患者CSF-αSyn-SAA扩增参数的差异。

方法

使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参数包括最大荧光强度（F）、达到F的50%的时间（T50）、达到阈值的时间（TTT）、斜率和曲线下面积（AUC）。散发性PD（n = 371）根据RBD和自主神经功能障碍（DysA）症状进行分层。遗传性PD包括GBA致病基因变异携带者（GBA-PD，n = 52）和LRRK2致病基因变异携带者（LRRK2-PD，n = 124）。

结果

CSF-αSyn-SAA在77%的LRRK2-PD、92.3%的GBA-PD和93.8%的散发性PD中呈阳性。与GBA-PD（分别为P = 0.029、P = 0.029、P = 0.016）和散发性PD（分别为P = 0.034、P = 0.033、P = 0.014）相比，LRRK2-PD队列的T50和TTT更长，AUC更小。在散发性队列中，有RBD（n = 157）和无RBD（n = 190）的PD患者之间CSF-αSyn-SAA参数相似，而有DysA（n = 193）的患者比无DysA（n = 150）的患者T50更短（P = 0.026），AUC更大（P = 0.029）。