McGeer P L, Walker D G, Pitas R E, Mahley R W, McGeer E G
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada.
Brain Res. 1997 Feb 21;749(1):135-8. doi: 10.1016/s0006-8993(96)01324-8.
Apolipoprotein E4 (ApoE4) increases the risk of late-onset Alzheimer's disease (AD). It binds tightly to beta-amyloid protein (A beta), which is known to activate the classical complement pathway in vitro. Since complement activation is a possible mechanism for promoting inflammation in AD, we tested, utilizing ELISA techniques, whether the various isoforms of ApoE could influence A beta complement activation, or could themselves activate the pathway. A beta applied alone to ELISA plate wells at concentrations of 100-500 ng showed a linear increase in ability to activate serum complement, but all the ApoE isoproteins were inactive. When 200 or 430 ng of A beta were plated and then exposed to solutions of 100-200 ng of ApoE2, ApoE3, ApoE4 or bovine serum albumin (BSA), only ApoE4 significantly enhanced the activation. This ApoE4-specific enhancement of complement activation by A beta may relate to its role in increasing the risk of late-onset AD.
载脂蛋白E4（ApoE4）会增加晚发性阿尔茨海默病（AD）的发病风险。它与β-淀粉样蛋白（Aβ）紧密结合，已知后者在体外可激活经典补体途径。由于补体激活是AD中促进炎症反应的一种可能机制，我们利用酶联免疫吸附测定（ELISA）技术检测了ApoE的各种异构体是否会影响Aβ补体激活，或者其自身是否能够激活该途径。单独以100 - 500 ng的浓度将Aβ加入ELISA板孔中时，其激活血清补体的能力呈线性增加，但所有ApoE同工蛋白均无活性。当将200或430 ng的Aβ铺板，然后暴露于100 - 200 ng的ApoE2、ApoE3、ApoE4或牛血清白蛋白（BSA）溶液中时，只有ApoE4显著增强了激活作用。ApoE4对Aβ补体激活的这种特异性增强作用可能与其在增加晚发性AD发病风险中的作用有关。
