CNS tau efflux via exosomes is likely increased in Parkinson's disease but not in Alzheimer's disease.

CNS tau efflux via exosomes is likely increased in Parkinson's disease but not in Alzheimer's disease.
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DOI:
10.1016/j.jalz.2016.04.003
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发表时间:
2016-11
期刊:
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子:
--
通讯作者:
Zhang J
Zhang J
中科院分区:
其他
文献类型:
--
作者:
Shi M;Kovac A;Korff A;Cook TJ;Ginghina C;Bullock KM;Yang L;Stewart T;Zheng D;Aro P;Atik A;Kerr KF;Zabetian CP;Peskind ER;Hu SC;Quinn JF;Galasko DR;Montine TJ;Banks WA;Zhang J

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阿尔茨海默病(AD)和帕金森病(PD)涉及tau病理学。在血液中可以检测到Tau蛋白,但人们对其在神经细胞和大脑中的清除作用知之甚少。通过在野生型和Tau敲除小鼠脑室内分别给予放射性标记的Tau和未标记的Tau来评估Tau从大脑向血液的外排。在含l1cam的外泌体中,中枢神经系统(CNS)衍生的tau进一步在人血浆中广泛表征,包括通过单分子阵列技术对303名受试者进行了研究。在小鼠中观察到Tau的外排,包括通过中枢神经系统衍生的L1CAM外泌体的一部分。在人血浆中,tau蛋白在L1CAM外泌体中被明确鉴定。与AD患者相比,PD患者的L1CAM外泌体tau显著高于对照组,且与脑脊液tau相关。Tau蛋白很容易从大脑运输到血液中。AD和PD的中枢神经系统tau外排机制可能不同。
Alzheimer disease (AD) and Parkinson disease (PD) involve tau pathology. Tau is detectable in blood, but its clearance from neuronal cells and the brain is poorly understood. 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. 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. Tau is readily transported from the brain to the blood. The mechanisms of CNS tau efflux are likely different between AD and PD.
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