Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation.
Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation.
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DOI：
10.1523/jneurosci.2610-10.2011
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发表时间：
2011-02-02
期刊：
影响因子：
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通讯作者：
Vargas-Caballero M
中科院分区：
文献类型：
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作者：
Shipton OA;Leitz JR;Dworzak J;Acton CE;Tunbridge EM;Denk F;Dawson HN;Vitek MP;Wade-Martins R;Paulsen O;Vargas-Caballero M
淀粉样β蛋白(Aβ)和tau蛋白都与轻度认知障碍和早期阿尔茨海默病(AD)的记忆障碍有关，但它们是否以及如何相互作用尚不清楚。因此，我们在这里询问是否需要tau蛋白来产生Aβ引起的海马长时程增强(LTP)损伤的强烈现象，LTP是一种广泛接受的记忆细胞模型。我们使用野生型小鼠和基因敲除tau蛋白的小鼠，并在急性切片准备中记录场电位。我们证明，缺乏tau蛋白可以阻止Aβ引起的长时程增强损伤。此外，我们还发现，Aβ可增加tau蛋白的磷酸化，而tau蛋白激酶的特异性抑制剂糖原合成酶激酶3(GSK-3)可阻断Aβ诱导的tau蛋白的磷酸化增加，并阻止Aβ对野生型小鼠长时程增强蛋白的损伤。综上所述，这些发现表明，tau蛋白是Aβ损伤海马区突触可塑性所必需的，并提示Aβ诱导的突触可塑性损伤是由tau磷酸化介导的。我们的结论是，阻止Aβ和tau之间的相互作用可能是治疗轻度认知障碍和早期阿尔茨海默病的一种有前途的策略。
Amyloid beta (Aβ) and tau protein are both implicated in memory impairment in mild cognitive impairment (MCI) and early Alzheimer’s disease (AD), but whether and how they interact is unknown. Consequently, here we asked if tau protein is required for the robust phenomenon of Aβ-induced impairment of hippocampal long-term potentiation (LTP), a widely accepted cellular model of memory. We used wild-type mice and mice with a genetic knockout of tau protein and recorded field potentials in an acute slice preparation. We demonstrate that the absence of tau protein prevents Aβ-induced impairment of LTP. Moreover, we show that Aβ increases tau phosphorylation and that a specific inhibitor of the tau kinase, glycogen synthase kinase 3 (GSK-3), blocks the increased tau phosphorylation induced by Aβ and prevents Aβ-induced impairment of LTP in wild-type mice. Together, these findings show that tau protein is required for Aβ to impair synaptic plasticity in the hippocampus and suggest that the Aβ-induced impairment of LTP is mediated by tau phosphorylation. We conclude that preventing the interaction between Aβ and tau could be a promising strategy for treating cognitive impairment in MCI and early AD.