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

Autor: Yaoyun Kuang, Hengxu Mao, Tingting Gan, Wenyuan Guo, Wei Dai, Weimeng Huang, Zhuohua Wu, Hongyan Li, Xiaoyun Huang, Xinling Yang, Ping-Yi Xu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: npj Parkinson's Disease, Vol 10, Iss 1, Pp 1-12 (2024)
Druh dokumentu: article
ISSN: 2373-8057
DOI: 10.1038/s41531-024-00738-7
Popis: 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.
Databáze: Directory of Open Access Journals