A skin-specific α-Synuclein seeding amplification assay for diagnosing Parkinson's disease.

IF 6.7 1区 医学 Q1 NEUROSCIENCES NPJ Parkinson's Disease Pub Date : 2024-07-04 DOI:10.1038/s41531-024-00738-7
Yaoyun Kuang, Hengxu Mao, Tingting Gan, Wenyuan Guo, Wei Dai, Weimeng Huang, Zhuohua Wu, Hongyan Li, Xiaoyun Huang, Xinling Yang, Ping-Yi Xu
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Abstract

The seeding amplification assay (SAA) has recently emerged as a valuable tool for detecting α-synuclein (αSyn) aggregates in various clinically accessible biospecimens. Despite its efficiency and specificity, optimal tissue-specific conditions for distinguishing Parkinson's disease (PD) from non-PD outside the brain remain underexplored. This study systematically evaluated 150 reaction conditions to identify the one with the highest discriminatory potential between PD and non-synucleinopathy controls using skin samples, resulting in a modified SAA. The streamlined SAA achieved an overall sensitivity of 92.46% and specificity of 93.33% on biopsy skin samples from 332 PD patients and 285 controls within 24 h. Inter-laboratory reproducibility demonstrated a Cohen's kappa value of 0.87 (95% CI 0.69-1.00), indicating nearly perfect agreement. Additionally, αSyn seeds in the skin were stable at -80 °C but were vulnerable to short-term exposure to non-ultra-low temperatures and grinding. This study thoroughly investigated procedures for sample preprocessing, seed amplification, and storage, introducing a well-structured experimental framework for PD diagnosis using skin samples.

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用于诊断帕金森病的皮肤特异性α-突触核蛋白播种扩增试验。
播种扩增试验(SAA)最近已成为检测各种临床生物样本中α-突触核蛋白(αSyn)聚集的重要工具。尽管该方法具有高效性和特异性,但区分帕金森病(PD)和脑外非帕金森病的最佳组织特异性条件仍未得到充分探索。本研究利用皮肤样本对 150 种反应条件进行了系统评估,以确定在帕金森病与非突触核蛋白病对照组之间具有最高鉴别潜力的反应条件,并由此产生了一种改进的 SAA。在 24 小时内对 332 名帕金森病患者和 285 名对照组患者的活检皮肤样本进行检测后,简化后的 SAA 的总体灵敏度为 92.46%,特异度为 93.33%;实验室间的重复性显示 Cohen's kappa 值为 0.87(95% CI 0.69-1.00),表明几乎完全一致。此外,皮肤中的αSyn种子在-80 °C下是稳定的,但短期暴露于非超低温和研磨条件下则很脆弱。这项研究对样本预处理、种子扩增和储存的程序进行了深入研究,为使用皮肤样本诊断白内障引入了一个结构合理的实验框架。
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来源期刊
NPJ Parkinson's Disease
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.
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