Department of Medicine Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Canada.
J Psychiatry Neurosci. 2013 Jan;38(1):6-23. doi: 10.1503/jpn.110190.
Alzheimer disease is the most prevalent form of dementia globally and is characterized premortem by a gradual memory loss and deterioration of higher cognitive functions and postmortem by neuritic plaques containing amyloid ß peptide and neurofibrillary tangles containing phospho-tau protein. Glutamate is the most abundant neurotransmitter in the brain and is essential to memory formation through processes such as long-term potentiation and so might be pivotal to Alzheimer disease progression. This review discusses how the glutamatergic system is impaired in Alzheimer disease and how interactions of amyloid ß and glutamate influence synaptic function, tau phosphorylation and neurodegeneration. Interestingly, glutamate not only influences amyloid ß production, but also amyloid ß can alter the levels of glutamate at the synapse, indicating that small changes in the concentrations of both molecules could influence Alzheimer disease progression. Finally, we describe how the glutamate receptor antagonist, memantine, has been used in the treatment of individuals with Alzheimer disease and discuss its effectiveness.
阿尔茨海默病是全球最常见的痴呆症形式，其生前表现为逐渐丧失记忆和高级认知功能的恶化，死后则表现为含有淀粉样β肽的神经纤维缠结和含有磷酸化tau 蛋白的神经原纤维缠结。谷氨酸是大脑中含量最丰富的神经递质，对于通过长时程增强等过程形成记忆至关重要，因此可能对阿尔茨海默病的进展起关键作用。本综述讨论了阿尔茨海默病中谷氨酸能系统如何受损，以及淀粉样β和谷氨酸的相互作用如何影响突触功能、tau 磷酸化和神经退行性变。有趣的是，谷氨酸不仅影响淀粉样β的产生，而且淀粉样β也可以改变突触处谷氨酸的水平，表明这两种分子浓度的微小变化可能会影响阿尔茨海默病的进展。最后，我们描述了谷氨酸受体拮抗剂美金刚如何用于治疗阿尔茨海默病患者，并讨论了其有效性。
