Acetylcholinesterase Accelerates Assembly of Amyloid-β-Peptides into Alzheimer's Fibrils: Possible Role of the Peripheral Site of the Enzyme

Abstract

Acetylcholinesterase (AChE), an important component of cholinergic synapses, colocalizes with amyloid-β peptide (Aβ) deposits of Alzheimer's brain. We report here that bovine brain AChE, as well as the human and mouse recombinant enzyme, accelerates amyloid formation from wild-type Aβ and a mutant Aβ peptide, which alone produces few amyloid-like fibrils. The action of AChE was independent of the subunit array of the enzyme, was not affected by edrophonium, an active site inhibitor, but it was affected by propidium, a peripheral anionic binding site ligand. Butyrylcholinesterase, an enzyme that lacks the peripheral site, did not affect amyloid formation. Furthermore, AChE is a potent amyloid-promoting factor when compared with other Aβ-associated proteins. Thus, in addition to its role in cholinergic synapses, AChE may function by accelerating Aβ formation and could play a role during amyloid deposition in Alzheimer's brain.