Microvascular injury and blood-brain barrier leakage in Alzheimer's disease
Microvascular injury and blood-brain barrier leakage in Alzheimer's disease
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DOI：
10.1016/j.neurobiolaging.2006.05.016
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发表时间：
2007-07-01
影响因子：
4.2
通讯作者：
Stopa, E. G.
中科院分区：
文献类型：
--
作者：
Zipser, B. D.;Johanson, C. E.;Stopa, E. G.
在阿尔茨海默病（AD）中，血管基底膜（VBM）变薄和不连续性与血浆蛋白凝血酶原穿过血脑屏障（BBB）渗漏有关。对前额皮质进行凝血酶原免疫组化和酶联免疫吸附测定。在严重的AD中，凝血酶原定位于微血管周围的壁和神经膜内。严重AD患者的因子VIII染色显示凝血酶原渗漏与内皮细胞收缩有关。酶联免疫吸附试验显示，前额皮质AD患者凝血酶原水平升高，随Braak分期升高（对照组= 1.39,I-II = 1.76, III-IV = 2.28, V-VI = 3.11 ng凝血酶原/mg总蛋白）。比较这四组，对照组和Braak V-VI期之间有显著差异（P = 0.0095）， Braak I-II期和V-VI期之间也有显著差异（P = 0.0048）。有与无脑淀粉样血管病（CAA）患者的平均凝血酶原水平比较无显著差异（p值= 0.3627）。在比较APOE基因型（ApoE3,3 = 2.00, ApoE3,4 = 2.49, ApoE4,4 = 2.96 ng凝血酶原/mg总蛋白）AD患者时，方差分析显示基因型间差异在10%显著水平（p = 0.0705）。Tukey的检验表明3,3和4,4组之间存在差异（p = 0.0607）。这些研究提供的证据表明，在晚期AD (Braak期V-VI)，血浆蛋白如凝血酶原可以在微血管壁和周围的神经血管中发现，并且血脑屏障的泄漏可能在至少有一个APOE4等位基因的患者中更常见。(C) 2006爱思唯尔公司版权所有。
Thinning and discontinuities within the vascular basement membrane (VBM) are associated with leakage of the plasma protein prothrombin across the blood-brain barrier (BBB) in Alzheimer's disease (AD). Prothrombin immunohistochemistry and ELISA assays were performed on prefrontal cortex. In severe AD, prothrombin was localized within the wall and neuropil surrounding microvessels. Factor VIII staining in severe AD patients indicated that prothrombin leakage was associated with shrinkage of endothelial cells. ELISA revealed elevated prothrombin levels in prefrontal cortex AD cases that increased with the Braak stage (Control = 1.39, I-II = 1.76, III-IV = 2.28, and V-VI = 3.11 ng prothrombin/mg total protein). Comparing these four groups, there was a significant difference between control and Braak V-VI (P = 0.0095) and also between Braak stages I-II and V-VI (p = 0.0048). There was no significant difference in mean prothrombin levels when cases with versus without cerebral amyloid angiopathy (CAA) were compared (p-value = 0.3627). When comparing AD patients by APOE genotype (ApoE3,3 = 2.00, ApoE3,4 = 2.49, and ApoE4,4 = 2.96 ng prothrombin/mg total protein) an analysis of variance indicated a difference between genotypes at the 10% significance level (p = 0.0705). Tukey's test indicated a difference between the 3,3 and 4,4 groups (p = 0.0607). These studies provide evidence that in advanced AD (Braak stage V-VI), plasma proteins like prothrombin can be found within the microvessel wall and surrounding neuropil, and that leakage of the blood-brain barrier may be more common in patients with at least one APOE4 allele. (C) 2006 Elsevier Inc. All rights reserved.