Chargé S B, Esiri M M, Bethune C A, Hansen B C, Clark A
Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, U.K.
J Pathol. 1996 Aug;179(4):443-7. doi: 10.1002/(SICI)1096-9896(199608)179:4<443::AID-PATH612>3.0.CO;2-7.
Apolipoprotein E (ApoE) has recently been proposed as an aetiological factor of Alzheimer's disease (AD): ApoE is co-localized to amyloid plaques and neurofibrillary tangles in the brain and binds to A beta-protein in vitro. An association of ApoE epsilon 4 allele with the development of AD has been reported. Islet amyloid is formed from islet amyloid polypeptide (IAPP) in pancreatic islets of 90 per cent of patients with non-insulin-dependent diabetes mellitus (NIDDM) which, like AD, is an age-dependent pathology. The relationship of ApoE to islet amyloid and other amyloidoses is largely unknown. In this study, ApoE was localized by immunocytochemistry on pancreatic specimens from non-diabetic man, monkey, and mouse, and on amyloid-containing human tissues from pancreas, heart, brain, and intestine. All types of amyloid deposits, irrespective of the constituent peptide, site of deposition, or species, showed immunoreactivity for ApoE (ApoE-IR). Quantitative morphometry showed that similar proportions of islet amyloid were labelled for IAPP and ApoE in monkey islets. ApoE-IR was observed in pancreatic islet cells of non-diabetics. These results suggest that the association of ApoE with amyloid is non-specific for AD or to the component peptide of amyloid fibrils. If ApoE promotes amyloid formation, its synthesis in pancreatic islets could be important for the initiation or the development of pancreatic amyloid in NIDDM.
载脂蛋白E（ApoE）最近被认为是阿尔茨海默病（AD）的一个病因：ApoE在大脑中的淀粉样斑块和神经原纤维缠结中共同定位，并且在体外与β-淀粉样蛋白结合。据报道，ApoE ε4等位基因与AD的发生有关。胰岛淀粉样变是由胰岛淀粉样多肽（IAPP）在90%的非胰岛素依赖型糖尿病（NIDDM）患者的胰岛中形成的，NIDDM与AD一样，是一种与年龄相关的病理状态。ApoE与胰岛淀粉样变及其他淀粉样变性的关系在很大程度上尚不清楚。在本研究中，通过免疫细胞化学方法对来自非糖尿病男性、猴子和小鼠的胰腺标本，以及来自胰腺、心脏、大脑和肠道的含淀粉样蛋白的人体组织进行ApoE定位。所有类型的淀粉样沉积物，无论其组成肽、沉积部位或物种如何，均显示对ApoE有免疫反应性（ApoE-IR）。定量形态学分析表明，在猴子胰岛中，标记IAPP和ApoE的胰岛淀粉样变比例相似。在非糖尿病患者的胰岛细胞中观察到ApoE-IR。这些结果表明，ApoE与淀粉样蛋白的关联并非AD或淀粉样纤维组成肽所特有的。如果ApoE促进淀粉样蛋白形成，那么它在胰岛中的合成对于NIDDM中胰腺淀粉样变的起始或发展可能很重要。
