Zhou Z, Smith J D, Greengard P, Gandy S
Laboratory of Alzheimer Research, Cornell University Medical College, New York, NY 10021, USA.
Mol Med. 1996 Mar;2(2):175-80.
The apolipoprotein E (apoE) type epsilon 4 isoform specifies increased cerebral and cerebrovascular accumulation of amyloid-beta protein (A beta) and contributes to the genetic susceptibility underlying a large proportion (approximately 60%) of typical, sporadic Alzheimer disease. Unfortunately, in vitro biochemical studies of direct apoE isoform-specific interactions with A beta have been inconsistent, perhaps due to the use by different research groups of apoE isoform preparations in different conformational states (purified denatured versus native).
In the current study, we have investigated the possibility that synthetic A beta(1-40) preferentially associates with native apoE of either the type epsilon 3 or the type epsilon 4 isoform.
Here, we demonstrate the preferential association of synthetic A beta(1-40) with native apoE epsilon 3. The complex between apoE epsilon 3 and A beta(1-40) could not be disrupted by sodium dodecyl sulfate. In a parallel assay, no denaturant-resistant association of A beta(1-40) with apoE epsilon 4 was detectable.
These results support the notion that the apoE epsilon 4 isoform may foster beta-amyloidogenesis because apoE epsilon 4 is inefficient in forming complexes with A beta.
载脂蛋白E（apoE）ε4亚型表明β淀粉样蛋白（Aβ）在大脑和脑血管中的积累增加，并且在很大比例（约60%）的典型散发性阿尔茨海默病的遗传易感性中起作用。不幸的是，关于apoE亚型与Aβ直接特异性相互作用的体外生化研究结果并不一致，这可能是由于不同研究小组使用了处于不同构象状态的apoE亚型制剂（纯化的变性型与天然型）。
在本研究中，我们研究了合成的Aβ（1-40）是否优先与ε3型或ε4型天然apoE结合的可能性。
在此，我们证明了合成的Aβ（1-40）与天然apoE ε3优先结合。apoE ε3与Aβ（1-40）之间的复合物不能被十二烷基硫酸钠破坏。在平行试验中，未检测到Aβ（1-40）与apoE ε4有抗变性剂的结合。
这些结果支持了apoE ε4亚型可能促进β淀粉样蛋白生成的观点，因为apoE ε4与Aβ形成复合物的效率较低。
