Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
Neurobiol Aging. 2012 May;33(5):1010.e1-13. doi: 10.1016/j.neurobiolaging.2011.10.022. Epub 2011 Nov 26.
The Arctic (p. E693G) mutation in the amyloid-β precursor protein (AβPP) facilitates amyloid-β (Aβ) protofibril formation and generates clinical symptoms of Alzheimer's disease (AD). Here, molecular details of Aβ in post mortem brain were investigated with biochemical and morphological techniques. The basic structure of Arctic plaques resembled cotton wool plaques. However, they appeared ring-formed with Aβ42-specific antibodies, but were actually targetoid, since the periphery and center of many parenchymal Aβ deposits stained differently with mid-domain, N- and C-terminal Aβ antibodies. Aβ fibrils were similar in shape, albeit shorter than in sporadic AD brain, when examined by electron microscopy. Aβwild-type and Aβarctic codeposited and parenchymal deposits were highly enriched in both N- and C-terminally truncated Aβ. In contrast, cerebral amyloid angiopathy (CAA) contained a substantial amount of Aβ1-40. The absence of plaques with cores of fibrillary Aβ might be due to the scarcity of full-length Aβ, although other mechanisms could be involved. Our findings are discussed in relation to mechanisms and relevance of amyloid formation and to the clinical features of AD.
淀粉样前体蛋白（AβPP）中的 Arctic（p.E693G）突变促进了淀粉样-β（Aβ）原纤维的形成，并产生了阿尔茨海默病（AD）的临床症状。在这里，使用生化和形态学技术研究了死后大脑中 Aβ 的分子细节。Arctic 斑块的基本结构类似于棉绒斑块。然而，它们与 Aβ42 特异性抗体一起呈环状形成，但实际上是靶状的，因为许多实质 Aβ 沉积物的外周和中心用中间结构域、N 端和 C 端 Aβ 抗体染色不同。电镜检查发现，Aβ 纤维的形状相似，尽管比散发性 AD 大脑中的纤维短。当 Aβ 野生型和 Aβ Arctic 共沉积时，实质沉积物中富含 N 端和 C 端截断的 Aβ。相比之下，脑淀粉样血管病（CAA）含有大量的 Aβ1-40。缺乏含有纤维状 Aβ 核心的斑块可能是由于全长 Aβ 的缺乏，尽管可能涉及其他机制。我们的发现与淀粉样形成的机制和相关性以及 AD 的临床特征有关。
