title: Dogs with Cognitive Dysfunction as a Spontaneous Model for Early Alzheimer's Disease: A Translational Study of Neuropathological and Inflammatory Markers.
abstract: Aged companion dogs with canine cognitive dysfunction (CCD) spontaneously develop varying degrees of progressive cognitive decline and particular neuropathological features correspondent to the changes associated with Alzheimer's disease (AD) in humans. The aim of the present study was to characterize certain aspects of neuropathology and inflammatory markers related to aging and CCD in dogs in comparison with human AD. Fifteen brains from aged dogs with normal cognitive function, mild cognitive impairment, or CCD were investigated and compared with two control brains from young dogs and brain sections from human AD subjects. The neuropathological investigations included evaluation of amyloid-β (Aβ) plaque deposition (N-terminally truncated and pyroglutamyl-modified Aβ included), tau pathology, and inflammatory markers in prefrontal cortex. Cortical Aβ deposition was found to be only of the diffuse subtype as no dense-core or neuritic plaques were found. The Aβ deposition followed a progressive pattern in four maturation stages. Accumulation of the Aβ peptide was also observed in the vessel walls. Both immunohistochemically and biochemically measured levels of Aβ pathology in prefrontal cortex showed a consistent positive correlation to age but not to cognitive deficit severity. No evidence of neurofibrillary tau pathology was found. The level of pro-inflammatory cytokines was generally low and showed no significant association to cognitive status. The findings of the present study support the senescent dog with spontaneous cognitive dysfunction as a valuable non-transgenic model for further investigations of the molecular events involved in the neurodegenerative processes associated with aging and early stage AD, especially the Aβ-related pathology.
authors.affiliation: Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.|Department of Neurodegeneration, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Schütt
authors.affiliation: Department of Neurodegeneration, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Lone
authors.initials: L
authors.lastname: Helboe
authors.affiliation: Department of Biologics, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Lars Østergaard
authors.initials: LØ
authors.lastname: Pedersen
authors.affiliation: Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Gunhild
authors.initials: G
authors.lastname: Waldemar
authors.affiliation: Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Berendt
authors.affiliation: Department of Neurodegeneration, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Jan Torleif
authors.initials: JT
authors.lastname: Pedersen
mesh_terms: D000375:Aging / Q000276:immunology / Q000473:pathology / Q000523:psychology; D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology; D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D060825:Cognitive Dysfunction / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003718:Denmark / Q000453:epidemiology; D004195:Disease Models, Animal; D018450:Disease Progression; D004283:Dog Diseases / Q000276:immunology / Q000473:pathology; D004285:Dogs; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008137:Longitudinal Studies; D008297:Male; D058225:Plaque, Amyloid / Q000276:immunology / Q000473:pathology; D012720:Severity of Illness Index; D013045:Species Specificity; D057170:Translational Research, Biomedical; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016207:Cytokines; D016875:tau Proteins
keywords: Aging; Alzheimer’s disease; amyloid-β; animal model; canine; dog; neurodegeneration