Cerebrospinal fluid from Alzheimer’s disease patients promotes tau aggregation in transgenic mice
Cerebrospinal fluid from Alzheimer’s disease patients promotes tau aggregation in transgenic mice
复制标题
阿尔茨海默病患者的脑脊液促进转基因小鼠中的 tau 蛋白聚集
DOI：
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发表时间：
2019
影响因子：
7.1
通讯作者：
D. Winkler
中科院分区：
文献类型：
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作者：
Z. Skachokova;Alfonso Martinisi;Martin Flach;F. Sprenger;Y. Naegelin;Viviane Steiner;M. Sollberger;A. Monsch;M. Goedert;M. Tolnay;D. Winkler
Tau是一种微管稳定蛋白，在阿尔茨海默病（AD）中形成聚集体。当注射到易感小鼠模型中时，来自AD患者脑的Tau以朊病毒样方式诱导Tau聚集。在这里，我们研究了从诊断为可能的AD或可能由于AD引起的轻度认知障碍（MCI）的患者收集的脑脊液（CSF）是否具有朊病毒样tau蛋白播种潜力。将CSF注射到P301S tau转基因小鼠的脑内。在接种后4个月，从AD或MCI患者获得的CSF增加了这些小鼠中海马tau过度磷酸化和tau缠结形成。在对侧海马中，以及在前后方向上，Tau病理学也加重，指示扩散。我们提供了AD患者CSF体内朊病毒样特性的第一个证据，加速了易感tau转基因小鼠的tau病理学。这表明生物活性tau种子到达AD中的CSF区室。进一步的研究可能有助于评估CSF衍生的tau生物种子的菌株特异性特性，并评估其诊断潜力。
Tau is a microtubule stabilizing protein that forms aggregates in Alzheimer’s disease (AD). Tau derived from AD patients’ brains induces tau aggregation in a prion-like manner when injected into susceptible mouse models. Here we investigated whether cerebrospinal fluid (CSF) collected from patients diagnosed with probable AD or mild cognitive impairment (MCI) likely due to AD harbors a prion-like tau seeding potential. CSF was injected intrahippocampally into young P301S tau transgenic mice. CSF obtained from AD or MCI patients increased hippocampal tau hyperphosphorylation and tau tangle formation in these mice at 4 months post-seeding. Tau pathology was also accentuated in the contralateral hippocampus, and in anterior and posterior directions, indicative of spreading. We provide first evidence for in vivo prion-like properties of AD patients’ CSF, accelerating tau pathology in susceptible tau transgenic mice. This demonstrates that biologically active tau seeds reach the CSF compartment in AD. Further studies may help to evaluate strain specific properties of CSF derived tau bioseeds, and to assess their diagnostic potential.
影响因子：
120.7
作者：
Sunderland, T;Linker, G;Cohen, RM
通讯作者：
Cohen, RM
影响因子：
2.1
作者：
Peskind E;Nordberg A;Darreh-Shori T;Soininen H
通讯作者：
Soininen H