Mann D M, Takeuchi A, Sato S, Cairns N J, Lantos P L, Rossor M N, Haltia M, Kalimo H, Iwatsubo T
Clinical Neuroscience Research Group, Department of Medicine, University of Manchester, UK.
Neuropathol Appl Neurobiol. 2001 Jun;27(3):189-96. doi: 10.1046/j.1365-2990.2001.00316.x.
The pattern of deposition of amyloid beta protein (Abeta) was investigated, using the monoclonal antibodies BA27 and BC05 detecting the C-terminal species Abeta40 and Abeta42(43), in six cases of Alzheimer's disease (AD) due to deletions in exon 9 of PS-1 gene. These cases are characterized histologically by the presence of very large rounded plaques within the frontal cortex, known as 'cotton wool' plaques, composed of both Abeta40 and Abeta42(43) that are relatively free from neuritic changes and glial cell components, and usually devoid of a compact amyloid core. In the cerebellum the plaques are almost entirely of a compact type, again composed of Abeta40 and Abeta42(43), with only few diffuse Abeta42(43) containing plaques. The area fraction of Abeta40, and the ratio between Abeta40 and Abeta42(43), in frontal cortex was significantly higher than that seen in other cases of AD due to different PS-1 mutations, or in cases of sporadic AD, all of similar APO E genotype. The area fractions of Abeta42(43), however, did not significantly differ between these three groups. The unusual nature of the Abeta deposition in these cases may reflect the uniqueness of the mutation, which results in a failure to constitutively cleave the PS-1 holoprotein into its active form, and the effect this might have on APP trafficking and catabolism.
利用检测C端片段β淀粉样蛋白40（Aβ40）和β淀粉样蛋白42（43）的单克隆抗体BA27和BC05，对6例因早老素1（PS - 1）基因第9外显子缺失导致的阿尔茨海默病（AD）患者的β淀粉样蛋白（Aβ）沉积模式进行了研究。这些病例在组织学上的特征是额叶皮质内存在非常大的圆形斑块，即所谓的“棉絮状”斑块，由Aβ40和Aβ42（43）组成，相对没有神经突改变和胶质细胞成分，且通常没有紧密的淀粉样核心。在小脑中，斑块几乎完全是紧密型的，同样由Aβ40和Aβ42（43）组成，只有少数含有弥散性Aβ42（43）的斑块。额叶皮质中Aβ40的面积分数以及Aβ40与Aβ42（43）的比值，显著高于因不同PS - 1突变导致的其他AD病例或散发性AD病例，所有这些病例的载脂蛋白E（APO E）基因型相似。然而，这三组中Aβ42（43）的面积分数没有显著差异。这些病例中Aβ沉积的异常性质可能反映了该突变的独特性，该突变导致无法将PS - 1全蛋白组成性切割成其活性形式，以及这可能对淀粉样前体蛋白（APP）的运输和分解代谢产生的影响。
