Effect of apolipoprotein AII on the interaction of apolipoprotein E with β‐amyloid: Some apo(E–AII) complexes inhibit the internalization of β‐amyloid in cultures of neuroblastoma cells

Apolipoprotein (apo) E and its polymorphism are linked to the pathogenesis of late‐onset and sporadic Alzheimer's disease (AD). ApoE facilitates the deposition and fibrillogenesis of β‐amyloid (Aβ), and may participate in Aβ clearance. We recently found that apo(E–AII) complex binds to Aβ much more strongly than does monomeric apoE. Here, we investigated the effect of apoAII on the interaction between apoE and Aβ. Addition of apoAII to apoE monomers increased the binding of apoE2 and apoE3 to Aβ 1–42 , presumably following the formation of apo(E3–AII), apo(E2–AII), and apo(AII–E2–AII) complexes. This increased binding was not seen in the case of apoE4. When neuroblastoma cells were cultured in media containing Aβ 1–42 and a mixture of apoE3 and apoAII, intracellular Aβ was significantly reduced and cell viability was maintained at a higher level than in cells cultured without apoAII. ApoE2 itself seemed to act as an inhibitor of the endocytosis of Aβ, and we did not observe a significant effect of apoAII on the movement of Aβ in apoE2‐containing medium. However, cell viability could be maintained at a higher level (as with apoE3) by adding apoAII to apoE2, despite the reduced viability of cells incubated without apoAII. In medium containing apoE4, both the amount of Aβ accumulated into cells and the cell viability were unchanged by the presence of apoAII in the medium. In addition, apoE4 itself was toxic, as previously suggested. These findings demonstrate that the type of apo(E–AII) complex present could underlie the isoform‐specific role of apoE in the pathogenesis of AD. J. Neurosci. Res. 62:608–614, 2000. © 2000 Wiley‐Liss, Inc.