Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain.
Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain.
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DOI：
10.1038/ncomms9490
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发表时间：
2015-10-13
影响因子：
16.6
通讯作者：
Hyman BT
中科院分区：
文献类型：
--
作者：
Takeda S;Wegmann S;Cho H;DeVos SL;Commins C;Roe AD;Nicholls SB;Carlson GA;Pitstick R;Nobuhara CK;Costantino I;Frosch MP;Müller DJ;Irimia D;Hyman BT
众所周知，在疾病进展过程中，tau 蛋白病理学在阿尔茨海默病 (AD) 大脑中以分层模式传播，可能是通过神经元之间的跨突触 tau 蛋白转移。然而，参与神经元间传播的 tau 蛋白种类仍不清楚。为了确定负责繁殖的 tau 物种，我们检查了来自 tau 转基因小鼠死后皮质提取物和脑间质液以及人类 AD 皮质的不同 tau 物种的摄取和繁殖特性。在这里，我们展示了 PBS 可溶性磷酸化高分子量 (HMW) tau，尽管丰度非常低，但却被吸收、轴突运输并传递到突触连接的神经元。我们的研究结果表明，一种罕见的可溶性磷酸化 HMW tau 蛋白是参与增殖的 tau 蛋白内源形式，可能成为治疗干预和生物标志物开发的目标。 在阿尔茨海默病中，tau 蛋白在整个大脑中扩散，但从一个神经元传播到另一个神经元的 tau 蛋白种类的性质尚不清楚。在这里，武田等人。鉴定出一种罕见的高分子量 tau 蛋白作为突触连接神经元之间吸收和转移的主要物种。
Tau pathology is known to spread in a hierarchical pattern in Alzheimer's disease (AD) brain during disease progression, likely by trans-synaptic tau transfer between neurons. However, the tau species involved in inter-neuron propagation remains unclear. To identify tau species responsible for propagation, we examined uptake and propagation properties of different tau species derived from postmortem cortical extracts and brain interstitial fluid of tau-transgenic mice, as well as human AD cortices. Here we show that PBS-soluble phosphorylated high-molecular-weight (HMW) tau, though very low in abundance, is taken up, axonally transported, and passed on to synaptically connected neurons. Our findings suggest that a rare species of soluble phosphorylated HMW tau is the endogenous form of tau involved in propagation and could be a target for therapeutic intervention and biomarker development. In Alzheimer's disease, tau spreads throughout the brain, however the nature of the tau species propagating from one neuron to another is not known. Here, Takeda et al. identify a rare, high-molecular-weight tau as the primary species taken up and transferred between synaptically connected neurons.