Inter-laboratory comparison of neuropathological assessments of β-amyloid protein:: a study of the BrainNet Europe consortium
Inter-laboratory comparison of neuropathological assessments of β-amyloid protein:: a study of the BrainNet Europe consortium
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DOI：
10.1007/s00401-008-0358-2
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发表时间：
2008-05-01
影响因子：
12.7
通讯作者：
Kretzschmar, Hans
中科院分区：
文献类型：
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作者：
Alafuzoff, Irina;Pikkarainen, Maria;Kretzschmar, Hans
淀粉样β蛋白(Aβ)通常由神经病理学家在诊断中进行评估。这项欧洲大脑网络(http://www.brainnet-europe.org/))(15个中心和26个参与者)的研究是为了调查这种评估的可靠性。在这项试验的第一部分，组织微阵列切片被每个中心选择的抗体染色。为了反映这一现实，使用了七种抗体和过多的预处理策略。92%的染色质量良好/可接受，对Aβ聚集体存在的估计产生了良好的结果。然而，在定量(密度)和定性(弥漫性/核心斑块)结果方面，尤其是达成了较差的一致性。在一次联席会议上，克隆4G8被确定为标记绒毛/弥漫斑块的最佳克隆，因此，该克隆和甲酸预处理技术被选为本研究的第二部分。随后，所有染色切片的质量良好/可接受，斑块和CAA的二分法(存在/不存在)评估再次达到高度一致。然而，即使只使用一种抗体，也不能可靠地指定Aβ聚集体的类型(弥漫性/核心)、血管类型和冯萨特尔分级。此外，对损伤的量化也远不可靠。与第一次试验一致，在评估密度(一些、中等和许多)时的一致性并不令人印象深刻。综上所述，我们可以肯定免疫组织化学检测Aβ蛋白在诊断和研究中的作用。值得注意的是，为了获得可重复性的结果，应该使用Aβ免疫反应性的二分法评估，而不是对各种类型的损伤进行量化和分配，特别是在比较不同神经病理学家获得的结果时。
Amyloid-beta-protein (A beta) is generally assessed by neuropathologists in diagnostics. This BrainNet Europe (http://www.brainnet-europe.org/) (15 centres and 26 participants) study was carried out to investigate the reliability of such an assessment. In the first part of this trial, tissue microarray sections were stained with the antibody of each centre's choice. Reflecting the reality, seven antibodies and a plethora of pretreatment strategies were used. Ninety-two percent of the stainings were of good/acceptable quality and the estimation of presence of A beta aggregates yielded good results. However, a poor agreement was reached particularly regarding quantitative (density) and qualitative (diffuse/cored plaques) results. During a joint meeting, the clone 4G8 was determined to label best the fleecy/diffuse plaques, and thus, this clone and the formic acid pretreatment technique were selected for the second part of this study. Subsequently, all stained sections were of good/acceptable quality and again a high level of concordance of the dichotomized (presence/absence) assessment of plaques and CAA was achieved. However, even when only one antibody was used, the type of A beta-aggregates (diffuse/cored), type of vessel and Vonsattel grade, were not reliably assigned. Furthermore, the quantification of lesions was far from reliable. In line with the first trial, the agreement while assessing density (some, moderate and many) was unimpressive. In conclusion, we can confirm the utility of immunohistochemical detection of A beta-protein in diagnostics and research. It is noteworthy that to reach reproducible results a dichotomized assessment of A beta-immunoreactivity rather than quantification and assignment of various types of lesions should be applied, particularly when comparing results obtained by different neuropathologists.