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Plasma Amyloid Beta Concentrations in Aged and Cognitively Impaired Pet Dogs

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Abstract

Longevity-associated neurological disorders have been observed across human and canine aging populations. Alzheimer’s disease (AD) and canine cognitive dysfunction syndrome (CDS) represent comparable diseases affecting both species as they age. Translational diagnostic and therapeutic research is needed for these incurable diseases. The amyloid β (Aβ) peptide family are AD-associated peptides with identical amino acid sequences between dogs and humans. Plasma Aβ42 concentration increases with age and decreases with AD in humans, and cerebrospinal fluid (CSF) concentration decreases in AD and correlates inversely with the amyloid load within the brain. Similarly, CSF Aβ42 concentrations decrease in dogs with CDS but there is limited and conflicting information on plasma Aβ42 concentrations in aging dogs and dogs with CDS. We measured plasma concentrations of Aβ42 and Aβ40 with an ultrasensitive single-molecule array assay (SIMOA) in a population of healthy aging dogs of different life stages (n = 36) and dogs affected with CDS (n = 11). In addition, the ratio of Aβ42/β40 was calculated. The mean plasma concentrations of Aβ42 and Aβ40 increased significantly with age (r2 = 0.27, p = 0.001; and r2 = 0.42, p < 0.001, respectively) and with life stage: puppy/junior group (0.43–2 years): 1.23 ± 0.95 and 38.26 ± 49.43 pg/mL; adult/mature group (2.1–9 years): 10.99 ± 5.45 and 131.05 ± 80.17 pg/mL; geriatric/senior group (9.3–14.5 years): 18.65 ± 16.65 and 192.88 ± 146.38 pg/mL, respectively. Concentrations of Aβ42 and Aβ40 in dogs with CDS (11.0–15.6 years) were significantly lower than age-matched healthy dogs at 11.61 ± 6.39 and 150.23 ± 98.2 pg/mL (p = 0.0048 and p = 0.001), respectively. Our findings suggest the dynamics of canine plasma amyloid concentrations are analogous to that found in aging humans with and without AD.

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Acknowledgments

We would like to acknowledge Quanterix company representatives for technical support. We want to thank dogs and their owners for taking part in the study.

Funding

This work is supported by the Dr. Kady M Gjessing and Rhanna M Davidson Distinguished Chair of Gerontology. F.M.M. is funded by NIH/NEI K08 EY028628.

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Authors and Affiliations

  1. Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA

    Wojciech K. Panek, Margaret E. Gruen, Freya M. Mowat & Natasha J. Olby

  2. Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA

    David M. Murdoch & Robert D. Marek

  3. Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA

    Freya M. Mowat

Authors
  1. Wojciech K. Panek
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  2. David M. Murdoch
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  3. Margaret E. Gruen
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  4. Freya M. Mowat
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  5. Robert D. Marek
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  6. Natasha J. Olby
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Contributions

W.K.P. and N J.O. conceived and designed the study, analyzed data, and wrote the manuscript. W.K.P performed experiments. W.K.P and R.D.D performed sample processing and testing. N.J.O., D.M. M., M.E. G, and F.M. M and provided critical feedback and oversaw the research program. All authors listed reviewed the manuscript and provided feedback with revisions.

Corresponding author

Correspondence to Natasha J. Olby.

Ethics declarations

All procedures were performed in accordance with the North Carolina State University Institutional Animal Care and Use Committee.

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The authors declare that they have no conflict of interest.

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ESM 1

The CADES score used to classify dogs as normal (0-7), mild (8-23), moderate (24-44) or severe (45-95) cognitive dysfunction. Seventeen items, distributed into four domains associated with behavioral changes (spatial orientation, social interactions, sleep-wake cycles and house soiling) were assessed. (TIF 1.98 mb)

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Panek, W.K., Murdoch, D.M., Gruen, M.E. et al. Plasma Amyloid Beta Concentrations in Aged and Cognitively Impaired Pet Dogs. Mol Neurobiol 58, 483–489 (2021). https://doi.org/10.1007/s12035-020-02140-9

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