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人脑β-淀粉样蛋白沉积的评估:欧洲脑网络联盟的一项研究。

Assessment of beta-amyloid deposits in human brain: a study of the BrainNet Europe Consortium.

作者信息

Alafuzoff Irina, Thal Dietmar R, Arzberger Thomas, Bogdanovic Nenad, Al-Sarraj Safa, Bodi Istvan, Boluda Susan, Bugiani Orso, Duyckaerts Charles, Gelpi Ellen, Gentleman Stephen, Giaccone Giorgio, Graeber Manuel, Hortobagyi Tibor, Höftberger Romana, Ince Paul, Ironside James W, Kavantzas Nikolaos, King Andrew, Korkolopoulou Penelope, Kovács Gábor G, Meyronet David, Monoranu Camelia, Nilsson Tatjana, Parchi Piero, Patsouris Efstratios, Pikkarainen Maria, Revesz Tamas, Rozemuller Annemieke, Seilhean Danielle, Schulz-Schaeffer Walter, Streichenberger Nathalie, Wharton Stephen B, Kretzschmar Hans

机构信息

Department of Clinical Medicine, Kuopio University, Finland.

出版信息

Acta Neuropathol. 2009 Mar;117(3):309-20. doi: 10.1007/s00401-009-0485-4. Epub 2009 Feb 1.

Abstract

beta-Amyloid (A-beta) related pathology shows a range of lesions which differ both qualitatively and quantitatively. Pathologists, to date, mainly focused on the assessment of both of these aspects but attempts to correlate the findings with clinical phenotypes are not convincing. It has been recently proposed in the same way as iota and alpha synuclein related lesions, also A-beta related pathology may follow a temporal evolution, i.e. distinct phases, characterized by a step-wise involvement of different brain-regions. Twenty-six independent observers reached an 81% absolute agreement while assessing the phase of A-beta, i.e. phase 1 = deposition of A-beta exclusively in neocortex, phase 2 = additionally in allocortex, phase 3 = additionally in diencephalon, phase 4 = additionally in brainstem, and phase 5 = additionally in cerebellum. These high agreement rates were reached when at least six brain regions were evaluated. Likewise, a high agreement (93%) was reached while assessing the absence/presence of cerebral amyloid angiopathy (CAA) and the type of CAA (74%) while examining the six brain regions. Of note, most of observers failed to detect capillary CAA when it was only mild and focal and thus instead of type 1, type 2 CAA was diagnosed. In conclusion, a reliable assessment of A-beta phase and presence/absence of CAA was achieved by a total of 26 observers who examined a standardized set of blocks taken from only six anatomical regions, applying commercially available reagents and by assessing them as instructed. Thus, one may consider rating of A-beta-phases as a diagnostic tool while analyzing subjects with suspected Alzheimer's disease (AD). Because most of these blocks are currently routinely sampled by the majority of laboratories, assessment of the A-beta phase in AD is feasible even in large scale retrospective studies.

摘要

β-淀粉样蛋白(A-β)相关病理学表现出一系列在性质和数量上都不同的病变。迄今为止,病理学家主要专注于对这两个方面的评估,但将这些发现与临床表型相关联的尝试并不令人信服。最近有人提出,与艾塔和α-突触核蛋白相关病变一样,A-β相关病理学可能也会遵循时间演变,即不同阶段,其特征是不同脑区逐步受累。26名独立观察者在评估A-β阶段时达成了81%的绝对一致,即阶段1 = A-β仅沉积于新皮层,阶段2 = 此外还沉积于异皮层,阶段3 = 此外还沉积于间脑,阶段4 = 此外还沉积于脑干,阶段5 = 此外还沉积于小脑。当至少评估六个脑区时,达成了这些高一致率。同样,在评估六个脑区时,在评估脑淀粉样血管病(CAA)的有无以及CAA的类型时(93%)也达成了高一致率(74%)。值得注意的是,当毛细血管CAA仅为轻度和局灶性时,大多数观察者未能检测到,因此诊断的不是1型CAA,而是2型CAA。总之,26名观察者通过检查仅取自六个解剖区域的一组标准化切片,应用市售试剂并按指示进行评估,实现了对A-β阶段以及CAA有无的可靠评估。因此,在分析疑似阿尔茨海默病(AD)的受试者时,人们可以将A-β阶段的评级视为一种诊断工具。由于目前大多数实验室通常会常规采集这些切片中的大多数,即使在大规模回顾性研究中,评估AD中的A-β阶段也是可行的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c302/2910889/629ad1c483a9/401_2009_485_Fig1_HTML.jpg

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