Many mouse models of Alzheimer's disease (AD) exhibit impairments in hippocampal long-term-potentiation (LTP), seemingly corroborating the strong correlation between synaptic loss and cognitive decline reported in human studies. In other AD mouse models LTP is unaffected, but other defects in synaptic plasticity may still be present. We recently reported that THY-Tau22 transgenic mice, that overexpress human Tau protein carrying P301S and G272 V mutations and show normal LTP upon high-frequency-stimulation (HFS), develop severe changes in NMDAR mediated long-term-depression (LTD), the physiological counterpart of LTP. In the present study, we focused on putative effects of AD-related pathologies on depotentiation (DP), another form of synaptic plasticity. Using a novel protocol to induce DP in the CA1-region, we found in 11-15 months old male THY-Tau22 and APPPS1-21 transgenic mice that DP was not deteriorated by Aß pathology while significantly compromised by Tau pathology. Our findings advocate DP as a complementary form of synaptic plasticity that may help in elucidating synaptic pathomechanisms associated with different types of dementia.

中文翻译：

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Tau病理而非Aß病理增强了AD小鼠模型中依赖于NMDAR的去势能力。

阿尔茨海默氏病（AD）的许多小鼠模型都表现出海马长时程增强（LTP）受损，似乎证实了人体研究中突触丧失与认知能力下降之间的强相关性。在其他AD小鼠模型中，LTP不受影响，但可能仍存在突触可塑性中的其他缺陷。我们最近报道说，THY-Tau22转基因小鼠过度表达带有P301S和G272 V突变的人类Tau蛋白，并在高频刺激（HFS）后显示正常LTP，在NMDAR介导的长期抑郁症（LTD）中发生了严重变化， LTP的生理对应物。在本研究中，我们集中于与AD有关的病理学对去势化（DP）（另一种形式的突触可塑性）的推定作用。使用新颖的协议在CA1区诱导DP，我们发现，在11-15个月大的雄性THY-Tau22和APPPS1-21转基因小鼠中，DP并未因Aß病理而恶化，而受到Tau病理的显着损害。我们的发现主张DP作为突触可塑性的一种补充形式，可能有助于阐明与不同类型痴呆症相关的突触病理机制。