BETA-AMYLOID PEPTIDES INCREASE THE BINDING AND INTERNALIZATION OF APOLIPOPROTEIN-E TO HIPPOCAMPAL-NEURONS

The frequency of the epsilon 4 allele oi apolipoprotein E (apoE) is in creased in late-onset and sporadic forms of Alzheimer's disease (AD). ApoE also binds to beta-amyloid (A beta) and both proteins are found i n AD plaques. To further investigate the potential interaction of apoE and A beta in the pathogenesis of AD, we have determined the binding, internalization, and degradation of human apoE isoforms in the presen ce and absence of A beta peptides to rat primary hippocampal neurons. We demonstrate that the lipophilic A beta peptides, in particular A be ta(1-42), A beta(1-40), and A beta(25-35), increase significantly apoE -liposome binding to hippocampal neurons. For each A beta peptide, the increase was significantly greater for the apoE4 isoform than for the apoE3 isoform. The most effective of the A beta peptides to increase apoE binding, A beta(25-35), was further shown to increase significant ly the internalization of both apoE3- and apoE4-liposomes, without aff ecting apoE degradation. Conversely, A beta(1-40) uptake by hippocampa l neurons was shown to be increased in tile presence of apoE-liposomes , more so in the presence of the apoE4, than the apoE3 isoform. These results provide evidence that A beta peptides interact directly with a poE lipoproteins, which may then be transported together into neuronal cells through apoE receptors.