α-Synuclein seeding amplification assays for diagnosing synucleinopathies: an innovative tool in clinical implementation.

IF 10.8 1区医学 Q1 NEUROSCIENCES Translational Neurodegeneration Pub Date : 2024-11-21 DOI:10.1186/s40035-024-00449-2

Yaoyun Kuang, Hengxu Mao, Xiaoyun Huang, Minshan Chen, Wei Dai, Tingting Gan, Jiaqi Wang, Hui Sun, Hao Lin, Qin Liu, Xinling Yang, Ping-Yi Xu

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Abstract

The spectrum of synucleinopathies, including Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), is characterized by α-synuclein (αSyn) pathology, which serves as the definitive diagnostic marker. However, current diagnostic methods primarily rely on motor symptoms that manifest years after the initial neuropathological changes, thereby delaying potential treatment. The symptomatic overlap between PD and MSA further complicates the diagnosis, highlighting the need for precise and differential diagnostic methods for these overlapping neurodegenerative diseases. αSyn misfolding and aggregation occur before clinical symptoms appear, suggesting that detection of pathological αSyn could enable early molecular diagnosis of synucleinopathies. Recent advances in seed amplification assay (SAA) offer a tool for detecting neurodegenerative diseases by identifying αSyn misfolding in fluid and tissue samples, even at preclinical stages. Extensive research has validated the effectiveness and reproducibility of SAAs for diagnosing synucleinopathies, with ongoing efforts focusing on optimizing conditions for detecting pathological αSyn in more accessible samples and identifying specific αSyn species to differentiate between various synucleinopathies. This review offers a thorough overview of SAA technology, exploring its applications for diagnosing synucleinopathies, addressing the current challenges, and outlining future directions for its clinical use.

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用于诊断突触核蛋白病的α-突触核蛋白种子扩增测定：临床应用中的创新工具。

突触核蛋白病包括帕金森病（PD）、多系统萎缩症（MSA）和路易体痴呆症（DLB），其病理特征是α-突触核蛋白（αSyn）病变，这是明确的诊断标志。然而，目前的诊断方法主要依赖于运动症状，而这些症状在最初的神经病理变化发生多年后才出现，从而延误了可能的治疗。帕金森病和多发性硬化症在症状上的重叠使诊断更加复杂，因此需要对这些重叠的神经退行性疾病采用精确的鉴别诊断方法。αSyn的错误折叠和聚集发生在临床症状出现之前，这表明病理αSyn的检测可以实现突触核蛋白病的早期分子诊断。种子扩增试验（SAA）的最新进展为检测神经退行性疾病提供了一种工具，它可以识别液体和组织样本中的αSyn错误折叠，甚至是在临床前阶段。广泛的研究已经验证了 SAA 诊断突触核蛋白病的有效性和可重复性，目前的工作重点是优化在更容易获得的样本中检测病理 αSyn 的条件，以及鉴定特定的 αSyn 种类以区分各种突触核蛋白病。本综述全面概述了 SAA 技术，探讨了其在诊断突触核蛋白病方面的应用，解决了当前面临的挑战，并概述了其临床应用的未来方向。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Neurodegeneration Neuroscience-Cognitive Neuroscience

CiteScore

19.50

自引率

0.80%

发文量

审稿时长

10 weeks

期刊介绍： Translational Neurodegeneration, an open-access, peer-reviewed journal, addresses all aspects of neurodegenerative diseases. It serves as a prominent platform for research, therapeutics, and education, fostering discussions and insights across basic, translational, and clinical research domains. Covering Parkinson's disease, Alzheimer's disease, and other neurodegenerative conditions, it welcomes contributions on epidemiology, pathogenesis, diagnosis, prevention, drug development, rehabilitation, and drug delivery. Scientists, clinicians, and physician-scientists are encouraged to share their work in this specialized journal tailored to their fields.