Deposition of amyloid plaques in limbic and associative cortices is amongst the most recognized histopathologic hallmarks of Alzheimer's disease. Despite decades of research, there is a lack of consensus over the impact of plaques on neuronal function, with their role in cognitive decline and memory loss undecided. Evidence has emerged suggesting complex and localized axonal pathology around amyloid plaques, with a significant fraction of swellings and dystrophies becoming enriched with putative synaptic vesicles and presynaptic proteins normally colocalized at hotspots of transmitter release. In the absence of hallmark active zone proteins and postsynaptic receptive elements, the axonal swellings surrounding amyloid plaques have been suggested as sites for ectopic release of glutamate, which under reduced clearance can lead to elevated local excitatory drive. Throughout this review, we consider the emerging data suggestive of amyloid plaques as hotspots of compulsive glutamatergic activity. Evidence for local and long-range effects of nonsynaptic glutamate is discussed in the context of circuit dysfunctions and neurodegenerative changes of Alzheimer's disease.

中文翻译：

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阿尔茨海默氏病的淀粉样蛋白斑作为谷氨酸能活性的热点。

边缘和相关皮质中淀粉样蛋白斑的沉积是阿尔茨海默氏病最公认的组织病理学标志之一。尽管进行了数十年的研究，但对于斑块对神经元功能的影响尚缺乏共识，因为斑块在认知功能减退和记忆力丧失中的作用尚未确定。已有证据表明，淀粉样蛋白斑周围是复杂的局部轴突病理，大量的肿胀和营养不良富含假定的突触小泡和突触前蛋白，这些蛋白通常共定位于递质释放的热点。在缺乏标志性活性区蛋白和突触后受体的情况下，淀粉样蛋白斑块周围的轴突肿胀被认为是谷氨酸异位释放的部位，在间隙减小的情况下会导致局部兴奋性驱动力升高。在整个审查过程中，我们认为新兴数据提示淀粉样蛋白斑是强迫性谷氨酸能活动的热点。在阿尔茨海默氏病的电路功能障碍和神经退行性变化的背景下讨论了非突触谷氨酸的局部和远距离影响的证据。