An investigation into the mechanisms mediating plasma lipoprotein-potentiated beta-amyloid fibrillogenesis.
The toxicity of the beta-amyloid (Abeta) peptide of Alzheimer's disease may relate to its polymerisation state (i.e. fibril content). We have shown previously that plasma lipoproteins, particularly when oxidised, greatly enhance Abeta polymerisation. In the present study the nature of the interactions between both native and oxidised lipoproteins and Abeta1-40 was investigated employing various chemical treatments. The addition of ascorbic acid or the vitamin E analogue, trolox, to lipoprotein/Abeta coincubations failed to inhibit Abeta fibrillogenesis, as did the treatment of lipoproteins with the aldehyde reductant, sodium borohydride. The putative lipid peroxide-derived aldehyde scavenger, aminoguanidine, however, inhibited Abeta-oxidised lipoprotein-potentiated polymerisation, but in a manner consistent with an antioxidant action for the drug. Lipoprotein treatment with the reactive aldehyde 4-hydroxy-2-trans-nonenal enhanced Abeta polymerisation in a concentration-dependent fashion. Incubation of Abeta with lipoprotein fractions from which the apoprotein components had been removed resulted in extents of polymerisation comparable to those observed with Abeta alone. These data indicate that the apoprotein components of plasma lipoproteins play a key role in promoting Abeta polymerisation, possibly via interactions with aldehydes.
Stanyer
Lee
L
Department of Medicine, Royal Free and University College Medical School, Sir Jules Thorn Institute, The Middlesex Hospital, Mortimer Street, W1N 8AA, London, UK.
Betteridge
D John
DJ
Smith
Christopher C T
CC
D000447:Aldehydes / Q000494:pharmacology; D000544:Alzheimer Disease / Q000209:etiology; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology; D001053:Apolipoproteins / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001704:Biopolymers / Q000096:biosynthesis; D001894:Borohydrides / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008074:Lipoproteins / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism*
D000447:Aldehydes; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001053:Apolipoproteins; D001704:Biopolymers; D001894:Borohydrides; D002839:Chromans; D006146:Guanidines; D008074:Lipoproteins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C025364:sodium borohydride; C027576:4-hydroxy-2-nonenal; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; C004479:pimagedine