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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome).
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Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome).

机译：阿尔茨海默氏病老年斑的定量分析：对数正态大小分布的观察和与载脂蛋白E基因型和21三体综合征（唐氏综合症）相关的分子流行病学观察。

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摘要

The discovery that the epsilon 4 allele of the apolipoprotein E (apoE) gene is a putative risk factor for Alzheimer disease (AD) in the general population has highlighted the role of genetic influences in this extremely common and disabling illness. It has long been recognized that another genetic abnormality, trisomy 21 (Down syndrome), is associated with early and severe development of AD neuropathological lesions. It remains a challenge, however, to understand how these facts relate to the pathological changes in the brains of AD patients. We used computerized image analysis to examine the size distribution of one of the characteristic neuropathological lesions in AD, deposits of A beta peptide in senile plaques (SPs). Surprisingly, we find that a log-normal distribution fits the SP size distribution quite well, motivating a porous model of SP morphogenesis. We then analyzed SP size distribution curves in genotypically defined subgroups of AD patients. The data demonstrate that both apoE epsilon 4/AD and trisomy 21/AD lead to increased amyloid deposition, but by apparently different mechanisms. The size distribution curve is shifted toward larger plaques in trisomy 21/AD, probably reflecting increased A beta production. In apoE epsilon 4/AD, the size distribution is unchanged but the number of SP is increased compared to apoE epsilon 3, suggesting increased probability of SP initiation. These results demonstrate that subgroups of AD patients defined on the basis of molecular characteristics have quantitatively different neuropathological phenotypes.
机译：载脂蛋白E（apoE）基因的epsilon 4等位基因是普通人群中阿尔茨海默氏病（AD）的推定危险因素的发现，突显了遗传因素在这种极为常见且致残的疾病中的作用。长期以来，人们已经认识到另一种遗传异常，即21三体综合征（唐氏综合症）与AD神经病理病变的早期和严重发展有关。然而，要理解这些事实与AD患者大脑中的病理变化之间的关系仍然是一个挑战。我们使用计算机图像分析来检查AD中特征性神经病理病变之一，老年斑（SPs）中Aβ肽的沉积物的大小分布。令人惊讶的是，我们发现对数正态分布非常适合SP大小分布，从而激发了SP形态发生的多孔模型。然后，我们分析了基因型定义的AD患者亚组的SP大小分布曲线。数据表明apoE epsilon 4 / AD和三体性21 / AD都导致淀粉样蛋白沉积增加，但机制明显不同。大小分布曲线在21 / AD三体症中移向更大的斑块，这可能反映了A beta产量的增加。在apoE epsilon 4 / AD中，大小分布没有变化，但是与apoE epsilon 3相比，SP的数量增加了，这表明SP启动的可能性增加了。这些结果表明，根据分子特征定义的AD患者亚组在数量上具有不同的神经病理学表型。

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