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首页> 外文期刊>Neurobiology of Aging: Experimental and Clinical Research >Structure and location of amyloid beta peptide chains and arrays in Alzheimer's disease: new findings require reevaluation of the amyloid hypothesis and of tests of the hypothesis.
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Structure and location of amyloid beta peptide chains and arrays in Alzheimer's disease: new findings require reevaluation of the amyloid hypothesis and of tests of the hypothesis.

机译：淀粉样蛋白β肽链和阵列在阿尔茨海默氏病中的结构和位置：新发现要求重新评估淀粉样蛋白假说和假说的检验。

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New in situ high resolution electronmicroscopic examination of amyloid fibrils in situ indicate that in Alzheimer's disease these fibrils are not simply long chains of self aggregated amyloid beta peptide. The amyloid beta is not only associated with P protein and glycans, as was well known from previous immunohistologic studies, but is arranged in the form of short chains at right angles to a P protein backbone with the glycans wrapped around that backbone. These findings suggest that the hypothesis causally relating simple, fibrillar amyloid beta to Alzheimer's disease must be reevaluated since such simple fibrils may be absent, or not the major form of the amyloid beta in the brain. Other data shows that shorter multimers, so-called protofibrils, or dimers of amyloid beta or molecules cleaved from it can be highly toxic. Some of these may be in the soluble amyloid beta fraction. Shorter multimers or dimers of amyloid beta, either extra or intracellular, may be the real links between amyloid beta production and Alzheimer's disease. Toxicity studies employing fibrillar amyloid beta may not be relevant, even if they produce lesions, because they do not employ amyloid beta in the form in which it actually exists in the Alzheimer brain. Studies of treatments designed to remove fibrils or to prevent their formation may be ineffective or suboptimal in effectiveness because they do not reduce the relevant amyloid burden and/or fail to alter the arrangement of shorter multimers of amyloid beta around its P-protein and glycan core.
机译：淀粉状蛋白原位的新的原位高分辨率电子显微镜检查表明，在阿尔茨海默氏病中，这些原纤维不仅仅是简单的自我聚集的淀粉样蛋白β肽的长链。如先前的免疫组织学研究所公知的，淀粉样蛋白β不仅与P蛋白和聚糖相关，而且以短链形式与P蛋白骨架成直角排列，聚糖包裹在该骨架上。这些发现表明，必须重新评估因简单的原纤维状淀粉样蛋白β与阿尔茨海默氏病而引起的假说，因为这种简单的原纤维可能不存在，或者不是大脑中淀粉样蛋白β的主要形式。其他数据表明，较短的多聚体（即所谓的原纤维）或淀粉样蛋白β的二聚体或从其裂解的分子可能具有很高的毒性。其中一些可能在可溶性淀粉样β馏分中。淀粉样蛋白β的较短的多聚体或二聚体（细胞外或细胞内）可能是淀粉样蛋白β产生与阿尔茨海默氏病之间的真正联系。即使使用纤维状淀粉样蛋白β进行毒性研究，即使它们会产生损害，也可能无关紧要，因为它们并未使用实际上存在于阿尔茨海默氏症脑中的淀粉样蛋白β。研究旨在去除原纤维或防止其形成的治疗方法可能无效或效果欠佳，因为它们不会减轻相关的淀粉样蛋白负担和/或无法改变淀粉样蛋白β较短的多聚体围绕其P蛋白和聚糖核心的排列方式。

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