Kida E, Choi-Miura N H, Wisniewski K E
New York State Institute for Basic Research in Developmental Disabilities, Department of Pathological Neurobiology, Staten Island 10314, USA.
Brain Res. 1995 Jul 10;685(1-2):211-6. doi: 10.1016/0006-8993(95)00482-6.
The link between the immunolocalization of apolipoproteins E (apo E) and J (apo J) and the different severity of beta-amyloid deposition in various areas of Alzheimer's disease (AD) and Down's syndrome (DS) brain was analyzed. Both apolipoproteins were found in all types of senile plaques (SPs) in the cerebral cortex, which is early and severely involved in beta-amyloidosis, but apo E was seen more often than apo J in diffuse A beta deposits, especially in young DS cases and nondemented elderly persons. In the striatum and cerebellum, which show predominance of diffuse A beta deposits throughout the lifespan, apo J was absent, except for few compact deposits, whereas apo E was more widely distributed, apart from diffuse plaques in the striatum. By immunoelectron microscopy, A beta fibrils were disclosed in diffuse plaques in all brain regions studied, but not all of these early fibrillar deposits, even in the neocortex of young DS cases, showed apo E and apo J labeling. Thus, our data indicate that the immunoreactivity to apo E and J within A beta deposits is topographically determined in both AD and DS brain. Moreover, although it appears that neither of apolipoproteins studied is necessary to initiate A beta fibrillogenesis, disclosed topographic dissimilarities of their distribution within parenchymal A beta deposits suggest that they may be involved in different ways in the pathogenesis of beta-amyloidosis.
分析了载脂蛋白E(apo E)和载脂蛋白J(apo J)的免疫定位与阿尔茨海默病(AD)和唐氏综合征(DS)大脑各区域β淀粉样蛋白沉积不同严重程度之间的联系。在大脑皮层中所有类型的老年斑(SPs)中均发现了这两种载脂蛋白,大脑皮层早期就严重受累于β淀粉样变性,但在弥漫性Aβ沉积物中apo E比apo J更常见,尤其是在年轻的DS病例和未患痴呆症的老年人中。在纹状体和小脑中,在整个生命周期中弥漫性Aβ沉积物占主导地位,除了少数致密沉积物外,未发现apo J,而apo E分布更广泛,纹状体中的弥漫性斑块除外。通过免疫电子显微镜观察,在所研究的所有脑区的弥漫性斑块中均发现了Aβ纤维,但并非所有这些早期纤维状沉积物,即使在年轻DS病例的新皮层中,都显示出apo E和apo J标记。因此,我们的数据表明,在AD和DS大脑中,Aβ沉积物内对apo E和J的免疫反应性是由地形决定的。此外,尽管似乎所研究的两种载脂蛋白都不是启动Aβ纤维形成所必需的,但在实质Aβ沉积物中它们分布的地形差异表明,它们可能以不同方式参与β淀粉样变性的发病机制。