A beta-peptide length and apolipoprotein E genotype in Alzheimer's disease
A beta-peptide length and apolipoprotein E genotype in Alzheimer's disease
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DOI：
10.1002/ana.410390320
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发表时间：
1996-03-01
影响因子：
11.2
通讯作者：
Mirra, SS
中科院分区：
文献类型：
--
作者：
Gearing, M;Mori, H;Mirra, SS
载脂蛋白E（ApoE）β 4等位基因是阿尔茨海默病（Alzheimer's disease，AD）的危险因子，与淀粉样蛋白沉积增加有关。我们使用不同长度的β-淀粉样蛋白（A β）肽（A β（1 - 40）和A β（1 - 42））的抗体检查了68例AD患者的大脑皮层，发现在α 4基因型中观察到的斑块频率增加可能主要归因于A β（1 - 40）阳性斑块的增加。事实上，A β（1 - 40）阳性斑块的数量，以及A β（1 - 40）/A β（1 - 42）阳性斑块的比例，均随剂量增加而增加。相比之下，A β（1 - 42）免疫反应性斑块的频率在β 3/β 3、β 3/β 4和β 4/β 4基因型中相似。ApoE可能通过促进A β（1 - 40）沉积到A β（1 - 42）接种的斑块上或通过调节由A β（1 - 42）原位形成A β（1 - 40）的假定羧肽酶的活性来影响A β长度。
Apolipoprotein E (ApoE) epsilon 4 allele, a risk factor for the development of Alzheimer's disease (AD), is associated with increased amyloid deposition. We examined cerebral cortex in 68 AD cases using antibodies to beta-amyloid (A beta) peptides of different length (A beta(1-40) and A beta(1-42)) and found that the increased plaque frequency observed with epsilon 4 genotypes may be largely attributed to an increase in A beta(1-40)-positive plaques. Indeed, both the number of A beta(1-40)-positive plaques, as web as the ratio Of A beta(1-40)/A beta(1-42)-positive plaques, increased with epsilon 4 dosage. In contrast, the frequency of A beta(1-42)-immunoreactive plaques was similar for epsilon 3/epsilon 3, epsilon 3/epsilon 4, and epsilon 4/epsilon 4 genotypes. ApoE may influence A beta length by facilitating A beta(1-40) deposition onto A beta(1-42)-seeded plaques or by modulating the activity of a putative carboxypeptidase that forms A beta(1-40) from A beta(1-42) in situ.