Neuronal Deposition of Amyloid-β Oligomers and Hyperphosphorylated Tau Is Closely Connected with Cognitive Dysfunction in Aged Dogs

Umma Habiba, Makiko Ozawa, James K. Chambers, Kazuyuki Uchida, Joseph Descallar, Hiroyuki Nakayama, Brian A. Summers, John W. Morley, Mourad Tayebi

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Background: Canine cognitive dysfunction (CCD) is a progressive syndrome recognized in mature to aged dogs with a variety of neuropathological changes similar to human Alzheimer's disease (AD), for which it is thought to be a good natural model. However, the presence of hyperphosphorylated tau protein (p-Tau) in dogs with CCD has only been demonstrated infrequently. Objective: The aim of the present study was to investigate the presence of p-Tau and amyloid-β oligomer (Aβo) in cerebral cortex and hippocampus of dogs with CCD, with focus on an epitope retrieval protocol to unmask p-Tau. Methods: Immunohistochemical and immunofluorescence analysis of the cortical and hippocampal regions of five CCD-affected and two nondemented aged dogs using 4G8 anti-Aβp, anti-Aβ1 - 42 nanobody (PrioAD13) and AT8 anti-p-Tau (Ser202, Thr205) antibody were used to demonstrate the presence of Aβ plaques (Aβp) and Aβ1 - 42 oligomers and p-Tau deposits, respectively. Results: The extracellular Aβ senile plaques were of the diffuse type which lack the dense core normally seen in human AD. While p-Tau deposits displayed a widespread pattern and closely resembled the typical human neuropathology, they did not co-localize with the Aβp. Of considerable interest, however, widespread intraneuronal deposition of Aβ1 - 42 oligomers were exhibited in the frontal cortex and hippocampal region that co-localized with p-Tau. Conclusion: Taken together, these findings reveal further shared neuropathologic features of AD and CCD, supporting the case that aged dogs afflicted with CCD offer a relevant model for investigating human AD.

Original languageEnglish
Pages (from-to)749-760
Number of pages12
JournalJournal of Alzheimer's Disease Reports
Volume5
Issue number1
DOIs
Publication statusPublished - 2021
Externally publishedYes

Keywords

  • Alzheimer's disease
  • amyloid-β plaques
  • Aβ1 - 42 oligomers
  • canine cognitive dysfunction
  • hyperphosphorylated tau

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