β-Amyloid fibrils catalyze neurotransmitter degradation

Summary 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 peptide (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 oxidation of the prominent neurotransmitters dopamine and adrenaline. Importantly, the catalytic activity was specifically manifested by mature Aβ42 fibrils and not the peptide monomers or oligomeric Aβ42, the putative neurotoxic species. Furthermore, maximal catalytic activity was recorded by the full-length Aβ42 fibrils, whereas fibrillar assemblies comprising Aβ42 subdomains were significantly less catalytic. The catalytic activity of Aβ fibrils could exhibit insidious roles in AD pathophysiology.