在一项涉及脑淀粉样血管病(CAA)研究兴趣的11个小组的合作中,我们采用两阶段流程制定了一项新的共识方案和评分方案,用于评估尸检脑组织中的CAA和相关血管病变异常.第一阶段使用迭代Delphi风格的调查来开发共识协议。所得到的评分方案在一系列数字图像和石蜡切片上进行测试,这些图像和石蜡切片被盲目地传播给多个评分者。通过公开论坛讨论,完善了评分方案和染色方法的选择。商定的方案以0-3量表对实质和脑膜CAA进行评分,毛细血管CAA存在/不存在和0-2量表上的血管病变,在分别评分的4个皮质叶中。然后进行了涉及三个中心的进一步评估。三个中心的神经病理学家(布里斯托尔,牛津和谢菲尔德)对75例病例(每个中心25例)的部分进行了独立评分,并证明了较高的评分者间可靠性。第二阶段使用三中心评估的结果,通过调查先前描述的APOE基因型(先前确定的)之间的关联来验证方案。以及CAA和血管病变。证实了毛细血管CAA有无小动脉CAA与APOEε4的关联。然而,APOEε2也被发现是CAA发展的重要危险因素,不仅在AD中,而且在老年人非痴呆对照中。鼓励进一步验证该方案和评分方案,以帮助其更广泛地采用,以促进CAA的协作和复制研究。
In a collaboration involving 11 groups with research interests in cerebral amyloid angiopathy (CAA), we used a two-stage process to develop and in turn validate a new
consensus protocol and scoring scheme for the assessment of CAA and associated vasculopathic abnormalities in post-mortem brain tissue. Stage one used an iterative Delphi-style survey to develop the
consensus protocol. The resultant scoring scheme was tested on a series of digital images and paraffin sections that were circulated blind to a number of scorers. The scoring scheme and choice of staining methods were refined by open-forum discussion. The agreed protocol scored parenchymal and meningeal CAA on a 0-3 scale, capillary CAA as present/absent and vasculopathy on 0-2 scale, in the 4 cortical lobes that were scored separately. A further assessment involving three centres was then undertaken. Neuropathologists in three centres (Bristol, Oxford and Sheffield) independently scored sections from 75 cases (25 from each centre) and high inter-rater reliability was demonstrated. Stage two used the results of the three-centre assessment to validate the protocol by investigating previously described associations between
APOE genotype (previously determined), and both CAA and vasculopathy. Association of capillary CAA with or without arteriolar CAA with
APOE ε4 was confirmed. However
APOE ε2 was also found to be a strong risk factor for the development of CAA, not only in AD but also in elderly non-demented controls. Further validation of this protocol and scoring scheme is encouraged, to aid its wider adoption to facilitate collaborative and replication studies of CAA.