β-Amyloid Fibrils are Biocatalytic

Amyloid fibrils are one of the hallmarks of Alzheimer's disease (AD), although a causative link between plaque-forming amyloid fibrils and AD pathology remains to be clarified. This study demonstrates, for the first time for a naturally occurring amyloid, that fibrils comprising the 42-residue Amyloid-β peptides (Aβ42) exhibit significant catalytic properties. Aβ42 fibrils catalyzed the hydrolysis of the model ester, para-nitrophenyl acetate (pNPA), and of acetylthiocholine, a surrogate for the neurotransmitter acetylcholine. Aβ42 fibrils also catalyzed the oxidation of the prominent neurotransmitters, dopamine and adrenaline. Importantly, the catalytic activity was specifically exhibited by mature Aβ42 fibrils, as opposed to the peptide monomers, or oligomeric Aβ42, the putative neurotoxic species. Importantly, maximal catalytic activity was exerted by the full-length Aβ42 fibrils, whereas fibrillar assemblies comprising Aβ42 subdomains exhibited significantly lower catalytic activity. The catalytic activity of Aβ fibrils may be implicated in pathophysiology pathways associated with the generation of AD amyloid plaques