Department of Psychiatry, Newcastle University, United Kingdom.
Ageing Res Rev. 2012 Jan;11(1):104-22. doi: 10.1016/j.arr.2011.06.004. Epub 2011 Jul 8.
In this review Alzheimer's disease is seen as a maladaptive interaction between human brain evolution and senescence. It is predicted to occur in everyone although does not necessarily lead to dementia. The pathological process is initiated in relation to a senescence mediated functional down-regulation in the posteromedial cortex (Initiation Phase). This leads to a loss of glutamatergic excitatory input to layer II entorhinal cortex neurons. A human specific maladaptive neuroplastic response is initiated in these neurons leading to neuronal dysfunction, NFT formation and death. This leads to further loss of glutamatergic excitatory input and propagation of the maladaptive response along excitatory pathways linking evolutionary progressed vulnerable neurons (Propagation Phase). Eventually neurons are affected in many brain areas resulting in dementia. Possible therapeutic approaches include enhancing glutamatergic transmission. The theory may have implications with regards to how Alzheimer's disease is classified.
在这篇综述中，阿尔茨海默病被视为人类大脑进化和衰老之间的一种适应不良的相互作用。尽管它并不一定会导致痴呆，但预计每个人都会发生这种疾病。病理过程是与衰老介导的后内侧皮质功能下调有关的（起始阶段）。这导致层 II 内嗅皮层神经元的谷氨酸能兴奋性输入丧失。在这些神经元中启动了一种人类特有的适应性神经可塑性反应，导致神经元功能障碍、NFT 形成和死亡。这导致沿着连接进化进展中脆弱神经元的兴奋性途径进一步丧失谷氨酸能兴奋性输入和适应性反应的传播（传播阶段）。最终，神经元会受到许多大脑区域的影响，导致痴呆。可能的治疗方法包括增强谷氨酸能传递。该理论可能对阿尔茨海默病的分类有影响。
