Beta-amyloid peptides increase the binding and internalization of apolipoprotein E to hippocampal neurons.
The frequency of the epsilon4 allele of apolipoprotein E (apoE) is increased in late-onset and sporadic forms of Alzheimer's disease (AD). ApoE also binds to beta-amyloid (A beta) and both proteins are found in 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 presence and absence of A beta peptides to rat primary hippocampal neurons. We demonstrate that the lipophilic A beta peptides, in particular A beta(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 significantly the internalization of both apoE3- and apoE4-liposomes, without affecting apoE degradation. Conversely, A beta(1-40) uptake by hippocampal neurons was shown to be increased in the 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 apoE lipoproteins, which may then be transported together into neuronal cells through apoE receptors.
Beffert
U
U
Douglas Hospital Research Centre, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Aumont
N
N
Dea
D
D
Lussier-Cacan
S
S
Davignon
J
J
Poirier
J
J
D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007536:Isomerism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats / Q000196:embryology; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010446:Peptide Fragments