Amyloid β protein deposition in patients with frontotemporal lobar degeneration:: relationship to age and apolipoprotein E genotype
Amyloid β protein deposition in patients with frontotemporal lobar degeneration:: relationship to age and apolipoprotein E genotype
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DOI：
10.1016/s0304-3940(01)01785-2
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发表时间：
2001-05-25
影响因子：
2.5
通讯作者：
Iwatsubo, T
中科院分区：
文献类型：
--
作者：
Mann, DMA;McDonagh, AM;Iwatsubo, T
应用六亚甲基四胺银染色和免疫组织化学方法对54例额颞叶变性（FTLD）尸检病例的额叶皮质中淀粉样β蛋白（AP）沉积进行了研究。在14例（26%）患者中检测到A β，几乎总是以弥漫性A β（42（43））的形式含有斑块，尽管偶尔观察到一些含有痕量A β（40）的核心神经炎斑块。14例显示AP沉积的患者在发病时明显比40例无A β的患者年龄大。54例病例中只有46例可以进行基因分型，其中16例携带至少一个载脂蛋白E（APOE）ε 4等位基因拷贝，等位基因频率为20%。APOE ε 4等位基因的携带与A β沉积显著相关，因此10/16的ε 4等位基因携带者具有A β沉积。这十名患者中有八名仅显示出轻度至中度的A β，但在两名患者（一名为epsilon 4等位基因纯合型，一名为epsilon 4等位基因杂合型）中，存在广泛的神经炎斑块和神经原纤维缠结形成。相反，只有少数非ε 4等位基因携带者（4/30）显示出轻微的A β沉积。当对APOE ε 4等位基因进行分层时，具有A β沉积的ε 4等位基因携带者和非携带者的发病年龄均显著晚于其各自的无A β沉积组。我们的结论是，A β沉积的可能性，作为一个次要的和巧合的功能无关的主要病理过程，在个体与FTLD的大脑将是高的，如果患者有足够晚的发病或碰巧是一个承载的APOE ε 4等位基因。事实上，在这里研究的14例A β沉积患者中，有9例在55岁以后发病，并携带APOE ε 4等位基因。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
Amyloid beta protein (AP) deposition was investigated in the frontal cortex of 54 autopsy cases of frontotemporal lobar degeneration (FTLD) using methenamine silver staining, and immunohistochemistry employing the monoclonal end-specific antibodies BC05 and BA27 to visualize deposits containing A beta (42(43)) and A beta (40), respectively. A beta was detected in 14 (26%) patients, nearly always in the form of diffuse A beta (42(43)) containing plaques though some cored, neuritic plaques with trace amounts of A beta (40) were occasionally seen. The 14 patients showing AP deposits were significantly older at onset of illness than those 40 patients without A beta. It was only possible to genotype 46/54 cases, 16 of whom bore at least one copy of the Apolipoprotein E (APOE) epsilon4 allele, giving an allele frequency of 20%. Possession of APOE epsilon4 allele was significantly associated with deposition of A beta such that 10/16 epsilon4 allele bearers had A beta deposits. Eight of these ten patients showed only mild to moderate amounts of A beta, but in two patients, one homozygous and one heterozygous for epsilon4 allele, there was extensive neuritic plaque and neurofibrillary tangle formation. In contrast, only few non-epsilon4 allele bearers (4/30) showed minor A beta deposits. When stratifying for APOE epsilon4 allele, both bearers and non-bearers of epsilon4 allele with A beta deposits had a significantly later age at onset than their respective groups without A beta deposits. We conclude that the likelihood of A beta deposition, as a secondary and coincidental feature unrelated to the primary pathological process, within the brains of individuals with FTLD will be high if patients have a sufficiently late onset of illness or happen to be a bearer of the APOE epsilon4 allele. Indeed 9/14 patients with A beta deposits studied here had an onset of illness after 55 years of age and bore APOE epsilon4 allele. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.