Rozemuller A J, Roos R A, Bots G T, Kamphorst W, Eikelenboom P, Van Nostrand W E
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Am J Pathol. 1993 May;142(5):1449-57.
Brain amyloidosis with abundant beta/A4 protein deposition in plaques and cortical and meningeal vessels is found in Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). In contrast to AD, no neuritic pathology or classical congophilic plaques are found in HCHWA-D. Unlike most AD cases, the congophilic angiopathy in HCHWA-D is very severe. It is still unknown whether beta/A4 deposits in plaques and vessels have the same origin. In this study, we have used frozen cortical tissue of HCHWA-D and AD patients to investigate the beta/A4 amyloid protein and the amyloid precursor protein (APP) in different types of plaques and congophilic angiopathy. Immunohistochemical staining was conducted using antibodies against synthetic beta/A4 proteins and antibodies against APP including MAbP2-1, a monoclonal antibody against purified protease nexin-2, which is the secreted form of APP. In contrast to immunohistochemical studies on formalin-fixed, paraffin-embedded tissue, frozen tissue of HCHWA-D patients revealed a very high number of beta/A4 plaques resembling AD. All plaques were of the diffuse type. Double-staining with MabP2-1 and beta/A4 antisera revealed: 1) the presence of APP immunoreactivity in classical plaques and transitional forms; 2) the absence of APP immunoreactivity in diffuse plaques in HCHWA-D and AD; and 3) pronounced APP immunoreactivity in congophilic vessels in HCHWA-D in contrast to weak APP staining in congophilic vessels in AD. Together these findings suggest that: a) the presence of APP in plaques is related to neuritic changes; b) different processes occur in amyloid formation in plaques and vessels; and c) differences exist between the process of amyloid formation in HCHWA-D and AD.
在阿尔茨海默病（AD）和荷兰型遗传性脑出血伴淀粉样变性（HCHWA-D）中可发现脑淀粉样变性，其在斑块以及皮质和脑膜血管中有大量β/A4蛋白沉积。与AD不同，HCHWA-D中未发现神经炎性病变或典型的嗜刚果红斑块。与大多数AD病例不同，HCHWA-D中的嗜刚果红血管病非常严重。尚不清楚斑块和血管中的β/A4沉积物是否具有相同的来源。在本研究中，我们使用HCHWA-D和AD患者的冷冻皮质组织来研究不同类型斑块和嗜刚果红血管病中的β/A4淀粉样蛋白和淀粉样前体蛋白（APP）。使用针对合成β/A4蛋白的抗体以及针对APP的抗体进行免疫组织化学染色，其中包括MAbP2-1，这是一种针对纯化的蛋白酶nexin-2的单克隆抗体，蛋白酶nexin-2是APP的分泌形式。与对福尔马林固定、石蜡包埋组织的免疫组织化学研究不同，HCHWA-D患者的冷冻组织显示出大量类似于AD的β/A4斑块。所有斑块均为弥漫型。用MabP2-1和β/A4抗血清进行双重染色显示：1）经典斑块和过渡形式中存在APP免疫反应性；2）HCHWA-D和AD的弥漫性斑块中不存在APP免疫反应性；3）与AD中嗜刚果红血管的APP染色较弱相比，HCHWA-D中嗜刚果红血管有明显的APP免疫反应性。这些发现共同表明：a）斑块中APP的存在与神经炎性变化有关；b）斑块和血管中淀粉样蛋白形成过程不同；c）HCHWA-D和AD的淀粉样蛋白形成过程存在差异。
