在帕金森病中，通过外泌体的中枢神经系统tau蛋白外流可能增加，但在阿尔茨海默病中并非如此。
CNS tau efflux via exosomes is likely increased in Parkinson's disease but not in Alzheimer's disease.
作者信息
Shi Min, Kovac Andrej, Korff Ane, Cook Travis J, Ginghina Carmen, Bullock Kristin M, Yang Li, Stewart Tessandra, Zheng Danfeng, Aro Patrick, Atik Anzari, Kerr Kathleen F, Zabetian Cyrus P, Peskind Elaine R, Hu Shu-Ching, Quinn Joseph F, Galasko Douglas R, Montine Thomas J, Banks William A, Zhang Jing
机构信息
Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA; Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
出版信息
Alzheimers Dement. 2016 Nov;12(11):1125-1131. doi: 10.1016/j.jalz.2016.04.003. Epub 2016 May 24.
INTRODUCTION
Alzheimer's disease (AD) and Parkinson's disease (PD) involve tau pathology. Tau is detectable in blood, but its clearance from neuronal cells and the brain is poorly understood.
METHODS
Tau efflux from the brain to the blood was evaluated by administering radioactively labeled and unlabeled tau intracerebroventricularly in wild-type and tau knock-out mice, respectively. Central nervous system (CNS)-derived tau in L1CAM-containing exosomes was further characterized extensively in human plasma, including by single molecule array technology with 303 subjects.
RESULTS
The efflux of Tau, including a fraction via CNS-derived L1CAM exosomes, was observed in mice. In human plasma, tau was explicitly identified within L1CAM exosomes. In contrast to AD patients, L1CAM exosomal tau was significantly higher in PD patients than controls and correlated with cerebrospinal fluid tau.
CONCLUSIONS
Tau is readily transported from the brain to the blood. The mechanisms of CNS tau efflux are likely different between AD and PD.
引言
阿尔茨海默病（AD）和帕金森病（PD）都涉及tau病理改变。tau在血液中可检测到，但其从神经元细胞和大脑中的清除机制尚不清楚。
方法
分别在野生型和tau基因敲除小鼠中，通过脑室内注射放射性标记和未标记的tau来评估tau从脑到血的流出情况。在人血浆中对含L1细胞黏附分子（L1CAM）的外泌体中源自中枢神经系统（CNS）的tau进行了广泛的进一步表征，包括对303名受试者采用单分子阵列技术。
结果
在小鼠中观察到tau的流出，包括一部分通过源自CNS的含L1CAM外泌体流出。在人血浆中，在含L1CAM的外泌体内明确鉴定出tau。与AD患者相比，PD患者中含L1CAM的外泌体tau显著高于对照组，且与脑脊液tau相关。
结论
tau很容易从脑转运到血液中。AD和PD中CNS tau流出的机制可能不同。
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