Departments of Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA.
N. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, Minnesota, USA.
J Neurochem. 2012 Jan;120 Suppl 1(Suppl 1):125-139. doi: 10.1111/j.1471-4159.2011.07478.x. Epub 2011 Nov 28.
For nearly 100 years following the first description of this neurological disorder by Dr Alois Alzheimer, amyloid plaques and neurofibrillary tangles have been hypothesized to cause neuronal loss. With evidence that the extent of insoluble, deposited amyloid poorly correlated with cognitive impairment, research efforts focused on soluble forms of Aβ, also referred as Aβ oligomers. Following a decade of studies, soluble oligomeric forms of Aβ are now believed to induce the deleterious cascade(s) involved in the pathophysiology of Alzheimer's disease. In this review, we will discuss our current understanding about endogenous oligomeric Aβ production, their relative toxicity in vivo and in vitro, and explore the potential future directions needed for the field.
近 100 年来，自 Alois Alzheimer 博士首次描述这种神经紊乱以来，淀粉样斑块和神经原纤维缠结一直被假设为导致神经元丧失的原因。由于证据表明不溶性、沉积的淀粉样蛋白与认知障碍的相关性较差，研究工作集中在可溶性形式的 Aβ上，也称为 Aβ寡聚物。经过十年的研究，现在认为可溶性寡聚形式的 Aβ会诱导阿尔茨海默病病理生理学中涉及的有害级联反应。在这篇综述中，我们将讨论我们目前对内源性寡聚 Aβ产生、它们在体内和体外的相对毒性的理解，并探讨该领域未来需要的潜在方向。
