title: Stable complexes involving acetylcholinesterase and amyloid-beta peptide change the biochemical properties of the enzyme and increase the neurotoxicity of Alzheimer's fibrils.
abstract: Brain acetylcholinesterase (AChE) forms stable complexes with amyloid-beta peptide (Abeta) during its assembly into filaments, in agreement with its colocalization with the Abeta deposits of Alzheimer's brain. The association of the enzyme with nascent Abeta aggregates occurs as early as after 30 min of incubation. Analysis of the catalytic activity of the AChE incorporated into these complexes shows an anomalous behavior reminiscent of the AChE associated with senile plaques, which includes a resistance to low pH, high substrate concentrations, and lower sensitivity to AChE inhibitors. Furthermore, the toxicity of the AChE-amyloid complexes is higher than that of the Abeta aggregates alone. Thus, in addition to its possible role as a heterogeneous nucleator during amyloid formation, AChE, by forming such stable complexes, may increase the neurotoxicity of Abeta fibrils and thus may determine the selective neuronal loss observed in Alzheimer's brain.
authors.affiliation: Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Alvarez
authors.forename: R
authors.initials: R
authors.lastname: Alarcón
authors.forename: C
authors.initials: C
authors.lastname: Opazo
authors.forename: E O
authors.initials: EO
authors.lastname: Campos
authors.forename: F J
authors.initials: FJ
authors.lastname: Muñoz
authors.forename: F H
authors.initials: FH
authors.lastname: Calderón
authors.forename: F
authors.initials: F
authors.lastname: Dajas
authors.forename: M K
authors.initials: MK
authors.lastname: Gentry
authors.forename: B P
authors.initials: BP
authors.lastname: Doctor
authors.forename: F G
authors.initials: FG
authors.lastname: De Mello
authors.forename: N C
authors.initials: NC
authors.lastname: Inestrosa
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D002642:Chick Embryo; D004795:Enzyme Stability; D016015:Logistic Models; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D009474:Neurons / Q000473:pathology*; D016716:PC12 Cells; D051381:Rats; D012995:Solubility
chemical_list: D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D000110:Acetylcholinesterase