Aluminium Mediated Glycosaminoglycan/Amyloid-β Association Mechanism

Abstract

In Alzheimer’s disease, it has been proposed that glycosaminoglycans facilitate amyloid fibril formation and/or stabilize the plaque aggregates. Chondroitin sulfates are sulfated glycosaminoglycans represented an ideal distribution of charge for amyloid-β (Aβ) interactions. Recent studies have suggested a possible link between the neurotoxicity of aluminum and the pathogenesis of Alzheimer’s disease. In this paper, the interaction of Aβ with chondroitin sulfates immobilized on a chromatographic column and the role of aluminum had been studied using a biochromatographic approach (molecular chromatography). A novel biochromatographic column was developed in our laboratory for studying this interaction. This study demonstrated that the aluminum interacted with Aβ and played a role in the Aβ/chondroitin sulfates association. For a Al3+ concentration (x) in the medium less than 30 μmM, the Aβ/chondroitin sulfates binding decreased with x due to a decrease of the charge–charge interactions between Aβ and its chondroitin sulfates binding site. Above 30 μmM of Al3+ in the medium, the affinity of Aβ to chondroitin sulfates increased slightly with x because the net number of ions (n) (Al3+ or Cl−) released or bound upon complex formation is low. As well, it was clearly demonstrated, that above 30 μmM the n value depend on the Al3+ concentration in the bulk solvent. This dependence was due to a gradual and conformational change of the Aβ which around 80 μmM adopted a less flexible structure; its binding site was thus less accessible to Aβ and Aβ/chondroitin sulfates association decreased slightly.