Alzheimer's and Parkinson's Disease Laboratory, Brain and Mind Research Institute, University of Sydney, Camperdown, NSW 2050, Australia.
Cell Mol Life Sci. 2011 Oct;68(20):3359-75. doi: 10.1007/s00018-011-0750-2. Epub 2011 Jun 25.
Alzheimer's disease (AD) is reaching epidemic proportions, yet a cure is not yet available. While the genetic causes of the rare familial inherited forms of AD are understood, the causes of the sporadic forms of the disease are not. Histopathologically, these two forms of AD are indistinguishable: they are characterized by amyloid-β (Aβ) peptide-containing amyloid plaques and tau-containing neurofibrillary tangles. In this review we compare AD to frontotemporal dementia (FTD), a subset of which is characterized by tau deposition in the absence of overt plaques. A host of transgenic animal AD models have been established through the expression of human proteins with pathogenic mutations previously identified in familial AD and FTD. Determining how these mutant proteins cause disease in vivo should contribute to an understanding of the causes of the more frequent sporadic forms. We discuss the insight transgenic animal models have provided into Aβ and tau toxicity, also with regards to mitochondrial function and the crucial role tau plays in mediating Aβ toxicity. We also discuss the role of miRNAs in mediating the toxic effects of the Aβ peptide.
阿尔茨海默病（AD）正在达到流行的程度，但还没有治愈的方法。虽然已经了解了罕见的家族遗传性 AD 形式的遗传原因，但该病散发性形式的原因尚不清楚。组织病理学上，这两种形式的 AD 无法区分：它们的特征是含有淀粉样β（Aβ）肽的淀粉样斑块和含有 Tau 的神经原纤维缠结。在这篇综述中，我们将 AD 与额颞叶痴呆（FTD）进行了比较，其中一部分以 Tau 沉积而没有明显斑块为特征。通过表达先前在家族性 AD 和 FTD 中发现的具有致病性突变的人类蛋白，已经建立了许多转基因动物 AD 模型。确定这些突变蛋白如何在体内引起疾病，应该有助于理解更常见的散发性形式的原因。我们讨论了转基因动物模型在 Aβ和 Tau 毒性方面提供的见解，还讨论了线粒体功能以及 Tau 在介导 Aβ毒性方面的关键作用。我们还讨论了 miRNA 在介导 Aβ肽的毒性作用中的作用。
