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

Brain-localized deposits of crystalline calcium phosphate, mainly comprising of hydroxyapatite, are a pathological hallmark of Alzheimer disease (AD). While calcium phosphate crystals are specifically identified in the neuronal amyloid plaques in AD, consisting mostly of beta amyloid (Aβ) 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 Aβ amyloid fibrils catalyze dephosphorylation of adenosine triphosphate (ATP). Furthermore, incubating Aβ fibrils, ATP, and calcium ions gave rise to pronounced deposition of hydroxyapatite crystals upon the Aβ 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.