Association of human, rat, and rabbit apolipoprotein E with β-amyloid

✍ Scribed by Mary Jo LaDu; John R. Lukens; Catherine A. Reardon; Godfrey S. Getz

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 238 KB
• Volume: 49
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19970701)49:1<9::aid-jnr2>3.0.co;2-h

✦ Synopsis

In humans, apolipoprotein E (apoE) has three major isoforms, E2 (Cys 112 , Cys 158 ), E3 (Cys 112 , Arg 158 ), and E4 (Arg 112 , Arg 158 ). While e4 is a genetic risk factor for Alzheimer's disease (AD), e2 may protect against late-onset AD. Using native preparations of apoE from conditioned tissue culture media or plasma lipoproteins, we have previously shown that when equivalent amounts of apoE3 or E4 were incubated with b-amyloid (Ab), apoE3 formed 20 times as much SDS-stable complex with the peptide as apoE4. This preferential binding of Ab to apoE3 was abolished when apoE was purified by a process which includes delipidation and denaturation. Here we expand these observations to include Ab binding to lipoprotein-associated and purified apoE2. Lipoproteins isolated from the plasma of individuals homozygous for either e2 or e3 were incubated with Ab(1-40). SDS-stable complex formation was analyzed by a non-reducing gel shift assay, followed by immunoblotting with either Ab or apoE antibodies. ApoE2:Ab complex formation was comparable to apoE3:Ab in both native and purified preparations of apoE. In addition, lipoprotein-associated rat apoE (Arg 112 , Arg 158 ), like human apoE4, did not form complex with Ab, while lipoprotein-associated rabbit apoE (Cys 112 , Arg 158 ) did bind the peptide. These binding studies provide one possible explanation for protective effects of both apoE2 and E3 against the development of Alzheimer's disease.