An investigation into the mechanisms mediating plasma lipoprotein-potentiated β-amyloid fibrillogenesis

Abstract

The toxicity of the β-amyloid (Aβ) 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 Aβ polymerisation. In the present study the nature of the interactions between both native and oxidised lipoproteins and Aβ 1–40 was investigated employing various chemical treatments. The addition of ascorbic acid or the vitamin E analogue, trolox, to lipoprotein/Aβ coincubations failed to inhibit Aβ fibrillogenesis, as did the treatment of lipoproteins with the aldehyde reductant, sodium borohydride. The putative lipid peroxide-derived aldehyde scavenger, aminoguanidine, however, inhibited Aβ-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 Aβ polymerisation in a concentration-dependent fashion. Incubation of Aβ with lipoprotein fractions from which the apoprotein components had been removed resulted in extents of polymerisation comparable to those observed with Aβ alone. These data indicate that the apoprotein components of plasma lipoproteins play a key role in promoting Aβ polymerisation, possibly via interactions with aldehydes.