title: Tau hyperphosphorylation in synaptosomes and neuroinflammation are associated with canine cognitive impairment.
abstract: Canine cognitive impairment syndrome (CDS) represents a group of symptoms related to the aging of the canine brain. These changes ultimately lead to a decline of memory function and learning abilities, alteration of social interaction, impairment of normal housetraining, and changes in sleep-wake cycle and general activity. We have clinically examined 215 dogs, 28 of which underwent autopsy. With canine brains, we performed extensive analysis of pathological abnormalities characteristic of human Alzheimer's disease and frontotemporal lobar degeneration, including β-amyloid senile plaques, tau neurofibrillary tangles, and fused in sarcoma (FUS) and TAR DNA-binding protein 43 (TDP43) inclusions. Most demented dogs displayed senile plaques, mainly in the frontal and temporal cortex. Tau neurofibrillary inclusions were found in only one dog. They were identified with antibodies used to detect tau neurofibrillary lesions in the human brain. The inclusions were also positive for Gallyas silver staining. As in humans, they were distributed mainly in the entorhinal cortex, hippocampus, and temporal cortex. On the other hand, FUS and TDP43 aggregates were not present in any of the examined brain samples. We also found that CDS was characterized by the presence of reactive and senescent microglial cells in the frontal cortex. Our transcriptomic study revealed a significant dysregulation of genes involved in neuroinflammation. Finally, we analyzed tau phosphoproteome in the synaptosomes. Proteomic studies revealed a significant increase of hyperphosphorylated tau in synaptosomes of demented dogs compared with nondemented dogs. This study suggests that cognitive decline in dogs is related to the tau synaptic impairment and neuroinflammation. J. Comp. Neurol. 524:874-895, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, 845 10, Bratislava, Slovak Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Smolek
authors.affiliation: University of Veterinary Medicine and Pharmacy, 040 01, Kosice, Slovak Republic.
authors.forename: Aladar
authors.initials: A
authors.lastname: Madari
authors.affiliation: University of Veterinary Medicine and Pharmacy, 040 01, Kosice, Slovak Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Farbakova
authors.affiliation: University of Veterinary Medicine and Pharmacy, 040 01, Kosice, Slovak Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Kandrac
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, 845 10, Bratislava, Slovak Republic.
authors.forename: Santosh
authors.initials: S
authors.lastname: Jadhav
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, 845 10, Bratislava, Slovak Republic.|Axon Neuroscience SE, 811 02, Bratislava, Slovak Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Cente
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, 845 10, Bratislava, Slovak Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Brezovakova
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, 845 10, Bratislava, Slovak Republic.|Axon Neuroscience SE, 811 02, Bratislava, Slovak Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Novak
authors.affiliation: Institute of Neuroimmunology, Slovak Academy of Sciences, 845 10, Bratislava, Slovak Republic.|Axon Neuroscience SE, 811 02, Bratislava, Slovak Republic.|Institute of Neuroimmunology, n.o., 811 02, Bratislava, Slovak Republic.
authors.forename: Norbert
authors.initials: N
authors.lastname: Zilka
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003072:Cognition Disorders / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004283:Dog Diseases / Q000378:metabolism* / Q000473:pathology; D004285:Dogs; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000378:metabolism / Q000473:pathology; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D015213:Neuroimmunomodulation / Q000502:physiology; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D034702:RNA-Binding Protein FUS / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D013574:Synaptosomes / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D034702:RNA-Binding Protein FUS; D016875:tau Proteins
keywords: canine cognitive impairment; dementia; microglia; neurofibrillary tangles; synapse; tau protein