Van Gool D, De Strooper B, Van Leuven F, Triau E, Dom R
Department of Neuropathology, University Hospital, Gasthuisberg, Leuven, Belgium.
Neurobiol Aging. 1993 May-Jun;14(3):233-7. doi: 10.1016/0197-4580(93)90006-w.
Because it has been suggested that alpha 2M could be involved in the generation of amyloid peptide, attention was given to a possible association of alpha 2M expression and amyloid accumulation in the brain. Therefore, we investigated the presence of the proteinase inhibitor alpha 2-macroglobulin (alpha 2M) in the cerebra of 4 patients with Alzheimer's Disease (AD). One case of a patient with Down's syndrome, 2 cases of patients with Dementia of the Lewy Body type (DLB), 1 case of an aged, clinically nondemented person who displayed many amyloid plaques, and 3 normal aged control brains were also studied. The results obtained by immunocytochemistry with monoclonal antibodies directed against two different epitopes of human alpha 2M showed an association of alpha 2M, only with neuritic-type plaques in patients with AD. No alpha 2M immunoreactivity was found in either preamyloid-type plaques or burned out-type plaques in AD, DLB, or aged nondemented controls. The results do not support a direct role of this proteinase inhibitor in the formation of amyloid. Because alpha 2M is observed to be associated with reactive microglia in the outer border of the neuritic plaques, the data suggest that alpha 2M could be a marker for an inflammatory cellular process in these neuritic plaques.
由于有人提出α2M可能参与淀粉样肽的生成，因此人们关注α2M表达与大脑中淀粉样蛋白积累之间的可能关联。因此，我们研究了4例阿尔茨海默病（AD）患者大脑中蛋白酶抑制剂α2-巨球蛋白（α2M）的存在情况。还研究了1例唐氏综合征患者、2例路易体痴呆型（DLB）患者、1例显示许多淀粉样斑块的老年非痴呆患者以及3个正常老年对照大脑。用针对人α2M两种不同表位的单克隆抗体进行免疫细胞化学检测所获得的结果显示，α2M仅与AD患者的神经炎性斑块相关。在AD、DLB或老年非痴呆对照的淀粉样前体斑块或耗竭型斑块中均未发现α2M免疫反应性。这些结果不支持这种蛋白酶抑制剂在淀粉样蛋白形成中起直接作用。由于观察到α2M与神经炎性斑块外缘的反应性小胶质细胞相关，数据表明α2M可能是这些神经炎性斑块中炎症细胞过程的标志物。
