Promotion of formation of amyloid fibrils by aluminium adenosine triphosphate (AlATP)

The formation of amyloid fibrils is considered to be an important step in t he aetiology of Alzheimer's disease and other amyloidoses. Fibril formation in vitro has been shown to depend on many different factors including modi fications to the amino acid profile of fibrillogenic peptides and interacti ons with both large and small molecules of physiological significance. How these factors might contribute to amyloid fibril formation in vivo is not c lear as very little is known about the promotion of fibril formation in und ersaturated solutions of amyloidogenic peptides. We have used thioflavin T fluorescence and reverse phase high performance liquid chromatography to sh ow that ATP. and in particular AIATP. promoted the formation of thioflavin T-reactive fibrils of beta amyloid and, an unrelated amyloidogenic peptide, amylin. Evidence is presented that induction of fibril formation followed the complexation of AlATP by one or more monomers of the respective peptide . However, the complex formed could not be identified directly and it is su ggested that AIATP might be acting as a chaperone in the assembly of amyloi d fibrils. The effect of AIATP was not mimicked by either AlADP or AlAMP. H owever, it was blocked by suramin, a P2 ATP receptor antagonist, and this h as prompted us to speculate that the precursor proteins to beta amyloid and amylin may be substrates or receptors for ATP in vivo. (C) 2001 Elsevier S cience B.V. All rights reserved.