基线脑脊液阴性的特发性快速眼动睡眠行为障碍患者中错误折叠α-突触核蛋白的纵向实时震动诱导转化分析
Longitudinal Real-Time Quaking-Induced Conversion Analysis of Misfolded α-Synuclein in Idiopathic Rapid Eye Movement Sleep Behavior Disorder Patients with Baseline Cerebrospinal Fluid Negativity.
文献信息
| PMID | 42947475 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Gerard Mayà |
| 作者单位 | Neurology Service, Sleep Centre, Hospital Clínic Barcelona, Universitat de Barcelona, IDIBAPS, CIBERNED: CB06/05/0018-ISCIII, Barcelona, Spain. |
| 期刊 | Movement disorders : official journal of the Movement Disorder Society |
| SCI 分区 | Q1 |
| IF | 8 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 耳科 |
中文摘要
背景： 虽然大多数特发性快速眼动睡眠行为障碍（IRBD）患者脑脊液错误折叠α-突触核蛋白呈阳性，但有一部分患者检测为阴性，其潜在基础尚不明确，可能包括非突触核蛋白病况。
目的与方法： 我们对经多导睡眠图确诊、基线脑脊液α-突触核蛋白阴性（LP1）并接受第二次腰椎穿刺（LP2）的IRBD患者进行了一项纵向研究。α-突触核蛋白的存在通过种子扩增试验确定。
结果： 在LP1时43例αSyn阴性患者中，9例（20.9%）在平均2.8±2.3年的随访期间转为αSyn阳性。在LP1时，与持续αSyn阴性患者相比，转换者表现出更高的帕金森病生物标志物负担，包括嗅觉减退、多巴胺转运体单光子发射计算机断层扫描（DAT-SPECT）异常以及快速眼动睡眠肌电活动增加。LP1与LP2之间间隔较长与αSyn转为阳性的比例较高相关。
结论： 系列脑脊液αSyn评估可能识别出非常早期的突触核蛋白病阶段。该策略可能改善针对αSyn的疾病修饰试验的患者选择。© 2026 International Parkinson and Movement Disorder Society。
英文摘要
BACKGROUND: While most patients with idiopathic REM sleep behavior disorder (IRBD) show CSF misfolded α-synucleinpositivity, a subset tests negative with an uncertain underlying substrate that may include non-synucleinopathy conditions.
OBJECTIVE AND METHODS: We performed a longitudinal study in polysomnography-confirmed IRBD patients with negative CSF α-synuclein at baseline (LP1) who underwent a second lumbar puncture (LP2). α-synuclein presence was determined by seed amplification assay.
RESULTS: Among 43 αSyn -negative patients at LP1, 9 (20.9%) converted to αSyn positivity over a mean follow-up of 2.8 ± 2.3 years. At LP1, converters exhibited a higher burden of Parkinson's disease biomarkers, including hyposmia, abnormal dopamine transporter single-photon emission computed tomography (DAT-SPECT), and increased REM sleep electromyographic activity, compared with patients with persistent αSyn negativity. Longer intervals between LP1 and LP2 were associated with higher αSyn shifting to positivity.
CONCLUSION: Serial CSF αSyn assessments may identify a very early synucleinopathy stage. This strategy may improve patient selection for disease-modifying trials targeting αSyn. © 2026 International Parkinson and Movement Disorder Society.