Hémar Agnès, Mulle Christophe
Institut interdisciplinaire de neurosciences, Université de Bordeaux, Bordeaux Cedex, France.
Med Sci (Paris). 2011 Aug-Sep;27(8-9):733-6. doi: 10.1051/medsci/2011278015. Epub 2011 Aug 31.
Alzheimer's disease (AD) is the first cause of dementia that leads to insidious and progressive loss of memory and cognitive functions. In the early stages of AD, there is a strong correlation between memory impairment and cortical levels of soluble amyloid-β peptide oligomers (Aβ). It has become clear that Aβ disrupt glutamatergic synaptic function, which in turn may lead to the characteristic cognitive deficits. Conversely, experiments in rodents have conforted the notion that Aβo impairs synaptic transmission and plasticity, and that mouse models with increased production of these oligomers display cognitive impairment. Many studies have attempted to determine the mechanisms by which Aβo disrupt synaptic plasticity and mediate their detrimental effect, but the actual pathways are still poorly understood. Here we review this thriving area of research which aims at understanding the mechanisms of synaptic dysfunction in the early phase of AD, and its consequences on the activity of neural circuits.
阿尔茨海默病（AD）是导致隐匿性和进行性记忆及认知功能丧失的首要痴呆病因。在AD的早期阶段，记忆障碍与可溶性淀粉样β肽寡聚体（Aβ）的皮质水平之间存在密切关联。现已明确，Aβ会破坏谷氨酸能突触功能，进而可能导致典型的认知缺陷。相反，啮齿动物实验证实了Aβ寡聚体（Aβo）会损害突触传递和可塑性这一观点，并且这些寡聚体产生增加的小鼠模型表现出认知障碍。许多研究试图确定Aβo破坏突触可塑性并介导其有害作用的机制，但实际途径仍知之甚少。在此，我们综述这一蓬勃发展的研究领域，其旨在了解AD早期阶段突触功能障碍的机制及其对神经回路活动的影响。
