Higher avidity binding of apolipoprotein (E–AII) complex than of apolipoprotein E monomer to β-amyloid

✍ Scribed by Kazuyoshi Yamauchi; Minoru Tozuka; Tetsuo Nakabayashi; Mitsutoshi Sugano; Hiroya Hidaka; Yoshiyuki Kondo; Tsutomu Katsuyama

• Book ID: 101244925
• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 120 KB
• Volume: 58
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19991015)58:2<301::aid-jnr10>3.0.co;2-9

✦ Synopsis

Apolipoprotein E (apoE) is believed to be closely involved in the pathogenesis of Alzheimer's disease (AD) because of its ability to bind to ␤-amyloid (A␤), the primary component of senile plaques. The presence of cystein residues in apoE2 and apoE3 allows these isoforms to form disulfide-linked complexes, such as apo(E-AII) complex and apo(AII-E-AII) complex. A 50-kDa complex [which corresponded to apo(E-AII)-A␤, because it reacted with any of the three antibodies, anti-apoE, anti-apoAII, or anti-A␤] was detected by immunoblot analysis in native cerebrospinal fluid (CSF) obtained from nondementia patients with the apoE phenotype E3/E3. However, a band considered to represent apoE-A␤ was not observed. The dissociation constant (Kd) values obtained for the specific binding of recombinant apoE2, apoE3, and apoE4 to A␤ 1-42 were 48.1 ؎ 2.2 nM, 63.7 ؎ 2.1 nM, and 75.9 ؎ 1.8 nM, respectively. In contrast, the binding affinity of the partially purified apo(E3-AII) complex to A␤ 1-42 was very high, the Kd being 5.5 ؎ 0.5 nM. No basic difference was observed between lipidated and nonlipidated apoE in terms of the characteristics of the binding of apoE isoforms to A␤ 1-42 ; however, lipidation reduced the binding capacity of each isoform in a dose-dependent manner. These findings seem consistent with the generally accepted idea that apoE4 is a risk factor for AD, insofar as only apoE4 is unable to form a complex with apoAII owing to its lack of a cystein residue. In addition, it is possible that apoE3 monomer (and possibly apoE2 monomer), like apoE4 but unlike apo(E-AII) complex, can act as a risk factor in the pathogenesis of AD.