Eikelenboom Piet, Veerhuis Rob, Familian Atoosa, Hoozemans Jeroen J M, van Gool Willem A, Rozemuller Annemieke J M
Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Neurodegener Dis. 2008;5(3-4):190-3. doi: 10.1159/000113699. Epub 2008 Mar 6.
The cerebral beta-amyloid (Abeta) disorders show a great variability in the distribution of parenchymal and vascular amyloid deposits.
To study the relationship between amyloid deposition and inflammatory responses in three distinct subtypes of cerebral Abeta disorders.
The distribution of inflammatory proteins and cells in vascular and plaque amyloid deposits was evaluated in postmortem brain tissue using immunohistochemistry. The effects of a mixture of Abeta peptides and inflammation-related Abeta-associated proteins were studied in postmortem obtained human microglia cell cultures.
The chronic inflammatory response is associated with amyloid plaques (but not with amyloid in the walls of larger vessels) in Alzheimer's disease (AD), with amyloid in cerebral arteries in hereditary cerebral hemorrhage with amyloidosis-Dutch type and with amyloid microangiopathy in the vascular variant of AD. Abeta(1-42) fibrils complexed with complement factor C1q and serum amyloid P component (the relevant amyloid-associated proteins) stimulate the production of proinflammatory cytokines in human microglia cell cultures and this production is attenuated by minocycline.
The pattern of the chronic inflammatory response associated with fibrillar Abeta is strikingly different in the three studied types of Abeta disorders. The site of the fibrillar Abeta-induced chronic inflammatory response is closely related to clinical symptoms. Minocycline is a drug of interest to inhibit microglia-mediated neuroinflammatory response in Abeta brain disorders.
脑β-淀粉样蛋白（Aβ）疾病在实质和血管淀粉样蛋白沉积的分布上表现出很大的变异性。
研究脑Aβ疾病三种不同亚型中淀粉样蛋白沉积与炎症反应之间的关系。
使用免疫组织化学方法在死后脑组织中评估血管和斑块淀粉样蛋白沉积物中炎症蛋白和细胞的分布。在死后获得的人小胶质细胞培养物中研究Aβ肽和炎症相关Aβ相关蛋白混合物的作用。
慢性炎症反应在阿尔茨海默病（AD）中与淀粉样斑块相关（但与较大血管壁中的淀粉样蛋白无关），在荷兰型遗传性脑出血伴淀粉样变性中与脑动脉中的淀粉样蛋白相关，在AD血管变体中与淀粉样微血管病相关。与补体因子C1q和血清淀粉样蛋白P成分（相关淀粉样蛋白相关蛋白）复合的Aβ（1-42）原纤维刺激人小胶质细胞培养物中促炎细胞因子的产生，而米诺环素可减弱这种产生。
在三种研究类型的Aβ疾病中，与纤维状Aβ相关的慢性炎症反应模式明显不同。纤维状Aβ诱导的慢性炎症反应部位与临床症状密切相关。米诺环素是一种有望抑制Aβ脑疾病中小胶质细胞介导的神经炎症反应的药物。
