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Canine Cognitive Dysfunction (CCD) scores correlate with amyloid beta 42 levels in dog brain tissue

Abstract

Alzheimer’s disease (AD) is a significant burden for human health that is increasing in prevalence as the global population ages. There is growing recognition that current preclinical models of AD are insufficient to recapitulate key aspects of the disease. Laboratory models for AD include mice, which do not naturally develop AD-like pathology during aging, and laboratory Beagle dogs, which do not share the human environment. In contrast, the companion dog shares the human environment and presents a genetically heterogeneous population of animals that might spontaneously develop age-associated AD-like pathology and cognitive dysfunction. Here, we quantitatively measured amyloid beta (Aβ42 or Abeta-42) levels in three areas of the companion dog brain (prefrontal cortex, temporal cortex, hippocampus/entorhinal cortex) and cerebrospinal fluid (CSF) using a newly developed Luminex assay. We found significant positive correlations between Aβ42 and age in all three brain regions. Brain Aβ42 abundance in all three brain regions was also correlated with Canine Cognitive Dysfunction Scale score in a multivariate analysis. This latter effect remained significant when correcting for age, except in the temporal cortex. There was no correlation between Aβ42 in CSF and cognitive scores; however, we found a significant positive correlation between Aβ42 in CSF and body weight, as well as a significant negative correlation between Aβ42 in CSF and age. Our results support the suitability of the companion dog as a model for AD and illustrate the utility of veterinary biobanking to make biospecimens available to researchers for analysis.

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Data availability

The full data used for this analysis are provided in Supplemental Table 1.

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Acknowledgements

The authors thank study participants, their dogs, and community veterinarians for their important contributions.

Funding

This work was supported by NIH grant 3U19AG057377-02S3 to DP. The Dog Aging Project is supported by U19 grant AG057377 from the National Institute on Aging, a part of the National Institutes of Health, and by private donations. The Senior Family Dog Project receives funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant Agreement No. 680040).

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Correspondence to Silvan R. Urfer.

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Enikő Kubinyi and Matt Kaeberlein jointly supervised this work.

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Urfer, S.R., Darvas, M., Czeibert, K. et al. Canine Cognitive Dysfunction (CCD) scores correlate with amyloid beta 42 levels in dog brain tissue. GeroScience (2021). https://doi.org/10.1007/s11357-021-00422-1

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Keywords

  • Dogs
  • Canine Cognitive Dysfunction
  • Abeta-42
  • Luminex
  • Alzheimer’s disease
  • Neurodegeneration
  • Age-related disease
  • Tissue banking