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ORIGINAL RESEARCH article

Front. Vet. Sci.
Sec. Veterinary Neurology and Neurosurgery
Volume 11 - 2024 | doi: 10.3389/fvets.2024.1390296
This article is part of the Research Topic Reviews in Veterinary Neurology and Neurosurgery View all 6 articles

Advancing the Early Detection of Canine Cognitive Dysfunction Syndrome with Machine Learning-Enhanced Blood-Based Biomarkers

Provisionally accepted
Chae Young Kim Chae Young Kim 1Jinhye Kim Jinhye Kim 2Sunmi Yoon Sunmi Yoon 2Isaac J. Yi Isaac J. Yi 3Hyuna Lee Hyuna Lee 4Sanghyuk Seo Sanghyuk Seo 5Dae Won Kim Dae Won Kim 6Soohyun Ko Soohyun Ko 7Sun-A Kim Sun-A Kim 8*Changhyuk Kwon Changhyuk Kwon 7*Sun Shin Yi Sun Shin Yi 10,2,9*
  • 1 BK21 Four Program, Department of Medical Sciences, Soonchunhyang University, Cheonan, South Chungcheong, Republic of Korea
  • 2 iCONNECTOME, Co., Ltd., Cheonan, South Chungcheong, Republic of Korea
  • 3 Department of Cognitive Science, School of Social Sciences, University of California, San Diego, La Jolla, California, United States
  • 4 iamdt, Co., Ltd., Seoul, Republic of Korea
  • 5 VIP Animal Medical Cencer, Seoul, Republic of Korea
  • 6 Department of Biochemistry and Molecular Biology, College of Dentstry, Gangneung-Wonju National University, Gangneung, Gangwon, Republic of Korea
  • 7 GenesisEgo, Co., Ltd., Seoul, Republic of Korea
  • 8 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States
  • 9 BK21 Four program, Department of Medical Sciences, Soonchunhyang University, Asan, Republic of Korea
  • 10 Department of Biomedical Laboratory Science, Soonchunhyang University, Asan, South Chungcheong, Republic of Korea

The final, formatted version of the article will be published soon.

    Up to half of the senior dogs suffer from canine cognitive dysfunction syndrome (CCDS), the diagnosis method relies on subjective questionnaires such as canine cognitive dysfunction rating (CCDR) scores. Therefore, the necessity of objective diagnosis is emerging. Here, we developed blood-based biomarkers for CCDS early detection. Blood samples from dogs with CCDR scores above 25 were analyzed, and the biomarkers retinol-binding protein 4 (RBP4), C-X-C-motif chemokine ligand 10 (CXCL10), and NADPH oxidase 4 (NOX4) were validated against neurodegenerative models. Lower biomarker levels were correlated with higher CCDR scores, indicating cognitive decline. Machinelearning analysis revealed the highest predictive accuracy when analyzing the combination of RBP4 and NOX4 using the support vector machine algorithm and confirmed potential diagnostic biomarkers. These results suggest that blood-based biomarkers can notably improve CCDS early detection and treatment, with implications for neurodegenerative disease management in both animals and humans.

    Keywords: biomarker, Blood-Brain Barrier, Canine cognitive dysfunction syndrome (CCDS), CCD rating scale (CCDR), C-X-C chemokine ligand 10, NADPH oxidase 4, Retinol binding protein 4, machine learning

    Received: 23 Feb 2024; Accepted: 30 Jul 2024.

    Copyright: © 2024 Kim, Kim, Yoon, Yi, Lee, Seo, Kim, Ko, Kim, Kwon and Yi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Sun-A Kim, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, 14853, New York, United States
    Changhyuk Kwon, GenesisEgo, Co., Ltd., Seoul, Republic of Korea
    Sun Shin Yi, BK21 Four program, Department of Medical Sciences, Soonchunhyang University, Asan, Republic of Korea

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.