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Distribution of tau hyperphosphorylation in canine dementia resembles early Alzheimer's disease and other tauopathies.

Authors
  • Abey, Ajantha1, 2
  • Davies, Danielle2, 3
  • Goldsbury, Claire2, 3
  • Buckland, Michael4, 5
  • Valenzuela, Michael1, 2, 6
  • Duncan, Thomas1, 2, 7
  • 1 Regenerative Neuroscience Group, The Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia. , (Australia)
  • 2 Discipline of Anatomy and Histology, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia. , (Australia)
  • 3 Alzheimer's Disease Cell Biology Research Lab, The Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia. , (Australia)
  • 4 Department of Neuropathology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. , (Australia)
  • 5 Sydney Medical School, Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia. , (Australia)
  • 6 School of Psychiatry, Medicine, University of New South Wales, Sydney, NSW, Australia. , (Australia)
  • 7 Department of Anatomy, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. , (Australia)
Type
Published Article
Journal
Brain Pathology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Aug 18, 2020
Identifiers
DOI: 10.1111/bpa.12893
PMID: 32810333
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Some aged community dogs acquire a degenerative syndrome termed Canine Cognitive Dysfunction (CCD) that resembles human dementia because of Alzheimer's Disease (AD), with comparable cognitive and behavioral deficits. Dogs also have similar neuroanatomy, share our domestic environment and develop amyloid-β plaques, making them likely a valuable ecological model of AD. However, prior investigations have demonstrated a lack of neurofibrillary tau pathology in aged dogs, an important hallmark of AD, though elevated phosphorylated tau (p-tau) at the Serine 396 (S396) epitope has been reported in CCD. Here using enhanced immunohistochemical methods, we investigated p-tau in six CCD brains and six controls using the AT8 antibody (later stage neurofibrillary pathology), and an antibody against S396 p-tau (earlier stage tau dysfunction). For the first time, we systematically assessed the Papez circuit and regions associated with Braak staging and found that all CCD dogs displayed elevated S396 p-tau labeling throughout the circuit. The limbic thalamus was particularly implicated, with a similar labeling pattern to that reported for AD neurofibrillary pathology, especially the anterior nuclei, while the hippocampus exhibited dysfunction confined to synaptic layers and efferent pathways. The cingulate and temporal lobes displayed significantly greater tauopathy than the frontal and occipital cortices, also reflective of early Braak staging patterns in AD. Immunofluorescence confirmed that S396 was accumulating within neuronal axons, somata and oligodendrocytes. We also observed AT8 labeling in one CCD brain, near the transentorhinal cortex in layer II neurons, one of the first regions to be affected in AD. Together, these data demonstrate a concordance in regional distribution of tauopathy between CCD and AD, most evident in the limbic thalamus, an important step in further validating CCD as a translational model for human AD and understanding early AD pathogenic mechanisms. © 2020 International Society of Neuropathology.

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