德国慕尼黑工业大学Arthur Konnerth研究团队取得一项新进展。他们的最新研究发现β-淀粉样蛋白依赖性神经元过度激活的恶性循环在阿尔兹海默症中的功能。2019年8月9日，国际知名学术期刊《科学》发表了这一成果。

研究人员使用Aβ-淀粉样变性的小鼠模型发现过度活跃通过抑制谷氨酸重新摄取来起始。过度活跃发生在具有预先存在的基线活跃的神经元中，而非活跃的神经元通常对Aβ介导的过度活跃具有抗性。含有Aβ的AD脑提取物和纯化的Aβ二聚体能够维持这种恶性循环。研究结果揭示了Aβ依赖性神经元功能障碍的细胞机制，其可能在斑块形成以前就起作用。

研究人员表示，β-淀粉样蛋白（Aβ）依赖性神经元过度活跃被认为是导致阿尔茨海默症（AD）早期阶段的回路功能障碍。尽管支持这一假设的实验证据仍在持续增加，但潜在的病理机制尚未得到很好的理解。

附：英文原文

Title: A vicious cycle of β amyloid–dependent neuronal hyperactivation

Author: Benedikt Zott, Manuel M. Simon, Wei Hong, Felix Unger, Hsing-Jung Chen-Engerer, Matthew P. Frosch, Bert Sakmann, Dominic M. Walsh, Arthur Konnerth

Issue&Volume: Vol. 365, Issue 6453, pp. 559-565

Abstract: β-amyloid (Aβ)–dependent neuronal hyperactivity is believed to contribute to the circuit dysfunction that characterizes the early stages of Alzheimer’s disease (AD). Although experimental evidence in support of this hypothesis continues to accrue, the underlying pathological mechanisms are not well understood. In this experiment, we used mouse models of Aβ-amyloidosis to show that hyperactivation is initiated by the suppression of glutamate reuptake. Hyperactivity occurred in neurons with preexisting baseline activity, whereas inactive neurons were generally resistant to Aβ-mediated hyperactivation. Aβ-containing AD brain extracts and purified Aβ dimers were able to sustain this vicious cycle. Our findings suggest a cellular mechanism of Aβ-dependent neuronal dysfunction that can be active before plaque formation.

DOI: 10.1126/science.aay0198

Source:https://science.sciencemag.org/content/365/6453/559