Amyloid-beta fibrils induce calcium phosphate crystallization via catalysis of ATP hydrolysis

Abstract

Brain-localized deposits of crystalline calcium phosphate, mainly comprising of hydroxyapatite, are a pathological hallmark of Alzheimers disease (AD). While calcium phosphate crystals are specifically identified in the neuronal amyloid plaques in AD, consisting mostly of beta amyloid (A{beta}) fibrils, the mechanisms and factors affecting the biomineralization are unknown. Here, we present a novel mechanism for AD plaque-induced formation of crystalline calcium phosphate. Specifically, we show, for the first time, that A{beta} amyloid fibrils catalyse dephosphorylation of adenosine triphosphate (ATP). Furthermore, incubating A{beta} fibrils, ATP, and calcium ions gave rise to pronounced deposition of hydroxyapatite crystals upon the A{beta} amyloid fibril matrix, originating through reaction between calcium ions and the monophosphate released through the catalytic dephosphorylation reaction. This pathway may explain amyloid plaque-associated calcification in AD, as elevated levels of both ATP and calcium are key features of the disease.