Gadhave Kundlik, Xu Enquan, Wang Ning, Zhang Xiaodi, Deyell Jacob, Yang Jun, Wang Anthony, Cha Youngjae, Kumbhar Ramhari, Liu Haiqing, Niu Lili, Chen Rong, Zhang Shu, Bakker Catherine C, Jin Lingtao, Liang Yajie, Ying Mingyao, Dawson Valina L, Dawson Ted M, Rosenthal Liana S, Mao Xiaobo
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
bioRxiv. 2024 Oct 24:2024.10.22.619694. doi: 10.1101/2024.10.22.619694.
α-Synuclein (α-syn) strains can serve as discriminators between Parkinson's disease (PD) from other α-synucleinopathies. The relationship between α-syn strain dynamics and clinical performance as patients transition from normal cognition (NC) to cognitive impairment (CI) is not known. Here, we show that the biophysical properties and neurotoxicity of α-syn strains change as PD cognitive status transitions from NC to mild cognitive impairment (PD-MCI) and dementia (PD-D). Both cross-sectional and longitudinal analyses reveal distinct α-syn strains in PD patients correlating to their level of cognitive impairment. This study presents evidence that individuals with PD have different α-syn strains that change in accordance with their cognitive status and highlights the potential of α-syn strain dynamics to guide future diagnosis, management, and stratification of PD patients.
α-突触核蛋白（α-syn）毒株可作为区分帕金森病（PD）与其他α-突触核蛋白病的鉴别标志物。目前尚不清楚在患者从正常认知（NC）转变为认知障碍（CI）的过程中，α-syn毒株动态变化与临床表现之间的关系。在此，我们表明，随着PD认知状态从NC转变为轻度认知障碍（PD-MCI）和痴呆（PD-D），α-syn毒株的生物物理特性和神经毒性会发生变化。横断面分析和纵向分析均显示，PD患者中存在与认知障碍程度相关的不同α-syn毒株。本研究提供的证据表明，患有PD的个体具有不同的α-syn毒株，这些毒株会根据其认知状态发生变化，并突出了α-syn毒株动态变化在指导未来PD患者诊断、管理和分层方面的潜力。
