title: Antibody against Small Aggregated Peptide Specifically Recognizes Toxic Aβ-42 Oligomers in Alzheimer's Disease.
abstract: Amyloid-beta (Aβ) oligomers have emerged as the most toxic species in Alzheimer's disease (AD) and other amyloid pathologies. Also, Aβ-42 peptide is more aggregation-prone compared to other Aβ isoforms. Thus, we synthesized a small peptide of repeated sequence containing the last three amino acids, Val-40, Ile-41, and Ala-42 of Aβ-42 that was subsequently aggregated and used to generate a novel antibody, VIA. In this study, we examined human AD and Tg2576 mouse brain samples using VIA in combination with other amyloid-specific antibodies and confirmed the specificity of VIA to oligomeric Aβ-42. Moreover, we found that VIA does not recognize classic amyloid plaques composed of fibrillar Aβ or Aβ-40 ex vivo. Since VIA recognizes a distinct epitope specific to Aβ-42 oligomers, it may have broad use for examining the accumulation of these oligomers in AD and other neurodegenerative diseases. VIA may also be used in immunotherapy studies to prevent neurodegenerative effects associated with Aβ-42 oligomers.
authors.affiliation: Mitchell Center for Neurodegenerative Diseases, ‡Departments of Neurology and Neuroscience and Cell Biology, §Department of Pharmacology and Toxicology, and ∥Sealy Center for Vaccine Development, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Riddhi U
authors.initials: RU
authors.lastname: Bodani
authors.affiliation: Mitchell Center for Neurodegenerative Diseases, ‡Departments of Neurology and Neuroscience and Cell Biology, §Department of Pharmacology and Toxicology, and ∥Sealy Center for Vaccine Development, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Urmi
authors.initials: U
authors.lastname: Sengupta
authors.affiliation: Mitchell Center for Neurodegenerative Diseases, ‡Departments of Neurology and Neuroscience and Cell Biology, §Department of Pharmacology and Toxicology, and ∥Sealy Center for Vaccine Development, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Castillo-Carranza
authors.affiliation: Mitchell Center for Neurodegenerative Diseases, ‡Departments of Neurology and Neuroscience and Cell Biology, §Department of Pharmacology and Toxicology, and ∥Sealy Center for Vaccine Development, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Guerrero-Muñoz
authors.affiliation: Mitchell Center for Neurodegenerative Diseases, ‡Departments of Neurology and Neuroscience and Cell Biology, §Department of Pharmacology and Toxicology, and ∥Sealy Center for Vaccine Development, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Gerson
authors.affiliation: Mitchell Center for Neurodegenerative Diseases, ‡Departments of Neurology and Neuroscience and Cell Biology, §Department of Pharmacology and Toxicology, and ∥Sealy Center for Vaccine Development, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Jai
authors.initials: J
authors.lastname: Rudra
authors.affiliation: Mitchell Center for Neurodegenerative Diseases, ‡Departments of Neurology and Neuroscience and Cell Biology, §Department of Pharmacology and Toxicology, and ∥Sealy Center for Vaccine Development, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: Rakez
authors.initials: R
authors.lastname: Kayed
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009447:Neuroblastoma / Q000473:pathology; D059906:Neuroimaging; D053764:Presenilin-1 / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D053764:Presenilin-1
keywords: Amyloid oligomers; repeated sequence; small peptide