title: Alzheimer's disease-like pathology induced by amyloid-β oligomers in nonhuman primates.
abstract: Alzheimer's disease (AD) is a devastating neurodegenerative disorder and a major medical problem. Here, we have investigated the impact of amyloid-β (Aβ) oligomers, AD-related neurotoxins, in the brains of rats and adult nonhuman primates (cynomolgus macaques). Soluble Aβ oligomers are known to accumulate in the brains of AD patients and correlate with disease-associated cognitive dysfunction. When injected into the lateral ventricle of rats and macaques, Aβ oligomers diffused into the brain and accumulated in several regions associated with memory and cognitive functions. Cardinal features of AD pathology, including synapse loss, tau hyperphosphorylation, astrocyte and microglial activation, were observed in regions of the macaque brain where Aβ oligomers were abundantly detected. Most importantly, oligomer injections induced AD-type neurofibrillary tangle formation in the macaque brain. These outcomes were specifically associated with Aβ oligomers, as fibrillar amyloid deposits were not detected in oligomer-injected brains. Human and macaque brains share significant similarities in terms of overall architecture and functional networks. Thus, generation of a macaque model of AD that links Aβ oligomers to tau and synaptic pathology has the potential to greatly advance our understanding of mechanisms centrally implicated in AD pathogenesis. Furthermore, development of disease-modifying therapeutics for AD has been hampered by the difficulty in translating therapies that work in rodents to humans. This new approach may be a highly relevant nonhuman primate model for testing therapeutic interventions for AD.
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis and Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil.
authors.forename: Leticia
authors.initials: L
authors.lastname: Forny-Germano
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis and.
authors.forename: Natalia M
authors.initials: NM
authors.lastname: Lyra e Silva
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis and.
authors.forename: André F
authors.initials: AF
authors.lastname: Batista
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis and.
authors.forename: Jordano
authors.initials: J
authors.lastname: Brito-Moreira
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis and.
authors.forename: Matthias
authors.identifier: http://orcid.org/0000-0002-0472-4263
authors.initials: M
authors.lastname: Gralle
authors.affiliation: Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Boehnke
authors.affiliation: Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Coe
authors.affiliation: Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Ann
authors.initials: A
authors.lastname: Lablans
authors.affiliation: Departament of Neurobiology, Institute of Biology, Fluminense Federal University, Niterói, RJ, 24020-140 Brazil, and.
authors.forename: Suelen A
authors.initials: SA
authors.lastname: Marques
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil.
authors.forename: Ana Maria B
authors.initials: AM
authors.lastname: Martinez
authors.affiliation: Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208.
authors.forename: William L
authors.initials: WL
authors.lastname: Klein
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil.
authors.forename: Jean-Christophe
authors.identifier: http://orcid.org/0000-0001-5128-438X
authors.initials: JC
authors.lastname: Houzel
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis and.
authors.forename: Sergio T
authors.initials: ST
authors.lastname: Ferreira
authors.affiliation: Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada, felice@bioqmed.ufrj.br doug.munoz@queensu.ca.
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Munoz
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis and felice@bioqmed.ufrj.br doug.munoz@queensu.ca.
authors.forename: Fernanda G
authors.initials: FG
authors.lastname: De Felice
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000473:pathology; D007276:Injections, Intraventricular; D008252:Macaca fascicularis; D008297:Male; D017628:Microglia / Q000473:pathology; D008845:Microinjections; D016874:Neurofibrillary Tangles / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; amyloid-β oligomers; nonhuman primate; synapse loss; tau pathology