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Publication

Tau hyperphosphorylation in synaptosomes and neuroinflammation are associated with canine cognitive impairment.

The Journal of comparative neurology | 2016

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.

Pubmed ID: 26239295 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

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Antibodies used in this publication

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This is a list of tools and resources that we have found mentioned in this publication.

Phospho-Tau (Ser262) Polyclonal Antibody (antibody)

RRID:AB_2533743

This polyclonal targets Phospho-Tau (Ser262)

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Drebrin antibody (antibody)

RRID:AB_2230303

This polyclonal targets DBN1

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Mouse Anti-Actin BSA and Azide Free Monoclonal Antibody, Unconjugated, Clone ACTN05; same as C4 (antibody)

RRID:AB_1523076

This monoclonal targets Actin

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Phospho-Tau (Ser396) Monoclonal Antibody (PHF13.6) (antibody)

RRID:AB_2533211

This monoclonal targets Phospho-Tau (Ser396)

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Phospho-Tau (Ser202, Thr205) Monoclonal Antibody (AT8) (antibody)

RRID:AB_223647

This monoclonal targets Phospho-Tau (Ser202, Thr205)

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Purified (azide-free) anti-beta-Amyloid, 17-24 (antibody)

RRID:AB_662812

This monoclonal targets beta-Amyloid 17-24

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Phospho-Tau (Thr205) Polyclonal Antibody (antibody)

RRID:AB_2533738

This polyclonal targets Phospho-Tau (Thr205)

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Phospho-Tau (Ser214) Polyclonal Antibody (antibody)

RRID:AB_2533740

This polyclonal targets Phospho-Tau (Ser214)

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Anti Iba1, Rabbit antibody (antibody)

RRID:AB_839504

This polyclonal targets Iba1

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Anti-Synaptophysin 1 (antibody)

RRID:AB_887822

This monoclonal targets Synaptophysin 1

View all literature mentions

Phospho-Tau (Thr231) Monoclonal Antibody (AT180) (antibody)

RRID:AB_223649

This monoclonal targets Phospho-Tau (Thr231)

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Phospho-Tau (Ser404) Polyclonal Antibody (antibody)

RRID:AB_2533746

This polyclonal targets Phospho-Tau (Ser404)

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GAP43 Antibody (antibody)

RRID:AB_10001196

This unknown targets GAP43

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Phospho-Tau (Ser199) Polyclonal Antibody (antibody)

RRID:AB_2533737

This polyclonal targets Phospho-Tau (Ser199)

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Phospho-Tau (Thr212) Polyclonal Antibody (antibody)

RRID:AB_2533739

This polyclonal targets Phospho-Tau (Thr212)

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Rabbit Anti-Human Tau, phospho (Thr217) Polyclonal Antibody, Unconjugated (antibody)

RRID:AB_1502121

This polyclonal targets Human Tau, phospho (Thr217)

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Anti-FUS (antibody)

RRID:AB_2571632

This polyclonal targets N-terminal region of human FUS isoform

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Advanced Image Data Analyzer (data processing software)

RRID:SCR_014440

Bioimaging analysis software used to acquire quantitative and qualitative data from various types of biological samples. The software provides a variety of image modification features, including contrast optimizing, image printing, 1-dimensional densitometry, fragment length and molecular weight determination, and 2-D densitometry.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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