Acetylcholinesterase accelerates assembly of amyloid-beta-peptides into Alzheimer's fibrils: possible role of the peripheral site of the enzyme

Neuron. 1996 Apr;16(4):881-91. doi: 10.1016/s0896-6273(00)80108-7.


Acetylcholinesterase (AChE), an important component of cholinergic synapses, colocalizes with amyloid-beta peptide (A beta) 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 A beta and a mutant A beta 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 A beta-associated proteins. Thus, in addition to its role in cholinergic synapses, AChE may function by accelerating A beta formation and could play a role during amyloid deposition in Alzheimer's brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Alzheimer Disease / enzymology*
  • Amyloid / metabolism
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Benzothiazoles
  • Binding Sites
  • Brain / enzymology*
  • Brain / ultrastructure
  • Butyrylcholinesterase / metabolism
  • Cattle
  • Fluorescent Dyes
  • Humans
  • Mice
  • Microscopy, Electron
  • Mutation
  • Neurofibrils / metabolism*
  • Neurofibrils / ultrastructure
  • Propidium / pharmacology
  • Recombinant Proteins / metabolism
  • Spectrometry, Fluorescence
  • Thiazoles / metabolism


  • Amyloid
  • Amyloid beta-Peptides
  • Benzothiazoles
  • Fluorescent Dyes
  • Recombinant Proteins
  • Thiazoles
  • thioflavin T
  • Propidium
  • Acetylcholinesterase
  • Butyrylcholinesterase