title: Evidence that a synthetic amyloid-ß oligomer-binding peptide (ABP) targets amyloid-ß deposits in transgenic mouse brain and human Alzheimer's disease brain.
abstract: The synthetic ~5 kDa ABP (amyloid-ß binding peptide) consists of a region of the 228 kDa human pericentrioloar material-1 (PCM-1) protein that selectively and avidly binds in vitro Aβ1-42 oligomers, believed to be key co-drivers of Alzheimer's disease (AD), but not monomers (Chakravarthy et al., (2013) [3]). ABP also prevents Aß1-42 from triggering the apoptotic death of cultured human SHSY5Y neuroblasts, likely by sequestering Aß oligomers, suggesting that it might be a potential AD therapeutic. Here we support this possibility by showing that ABP also recognizes and binds Aβ1-42 aggregates in sections of cortices and hippocampi from brains of AD transgenic mice and human AD patients. More importantly, ABP targets Aβ1-42 aggregates when microinjected into the hippocampi of the brains of live AD transgenic mice.
authors.affiliation: Human Health Therapeutics, National Research Council of Canada, Ottawa, Ontario, Canada. Electronic address: Balu.Chakravarthy@nrc-cnrc.gc.ca.
authors.forename: Balu
authors.initials: B
authors.lastname: Chakravarthy
authors.affiliation: Human Health Therapeutics, National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: Shingo
authors.initials: S
authors.lastname: Ito
authors.affiliation: Human Health Therapeutics, National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: Trevor
authors.initials: T
authors.lastname: Atkinson
authors.affiliation: Human Health Therapeutics, National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: Chantal
authors.initials: C
authors.lastname: Gaudet
authors.affiliation: Human Health Therapeutics, National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Ménard
authors.affiliation: Human Health Therapeutics, National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: Leslie
authors.initials: L
authors.lastname: Brown
authors.affiliation: Human Health Therapeutics, National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Whitfield
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding
chemical_list: D016229:Amyloid beta-Peptides; D001324:Autoantigens; D018797:Cell Cycle Proteins; C086074:PCM1 protein, human; D010446:Peptide Fragments; D010455:Peptides; C075222:amyloid beta-protein (1-42)
keywords: AD transgenic mice; Alzheimer’s disease; Amyloid binding peptide; Aβ(1–42) oligomers; Human AD brains; PCM-1 protein