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)
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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DOI：
10.1073/pnas.92.8.3586
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发表时间：
1995-04-11
影响因子：
11.1
通讯作者：
STANLEY, HE
中科院分区：
文献类型：
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作者：
HYMAN, BT;WEST, HL;STANLEY, HE
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病（AD）的一个假定的危险因素，这一发现突出了遗传影响在这种极其常见和致残疾病中的作用。人们早就认识到，另一种遗传异常，21三体（唐氏综合征），与阿尔茨海默病神经病理病变的早期和严重发展有关。然而，了解这些事实与阿尔茨海默病患者大脑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的一个特征性神经病理病变的大小分布，老年斑（SPs）中的A - β肽沉积，令人惊讶的是，我们发现对数正态分布非常适合SP的大小分布，从而推动了SP形态发生的多孔模型。然后，我们分析了基因典型定义的AD患者亚组的SP大小分布曲线。数据表明apoE epsilon 4/AD和21三体/AD均导致淀粉样蛋白沉积增加，但其机制明显不同。在21三体/AD中，斑块的大小分布曲线向较大的斑块偏移，这可能反映了A β产生的增加。在apoE epsilon 4/AD中，斑块的大小分布不变，但SP的数量比apoE epsilon 3增加，提示SP发生的概率增加。这些结果表明，基于分子特征定义的AD患者亚组具有定量不同的神经病理表型。
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.