Plasma Neurofilament Light Chain as a Translational Biomarker of Aging and Neurodegeneration in Dogs
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ORIGINAL ARTICLE
Plasma Neurofilament Light Chain as a Translational Biomarker of Aging and Neurodegeneration in Dogs Wojciech K. Panek 1 & Margaret E. Gruen 1 & David M. Murdoch 2 & Robert D. Marek 2 & Alexandra F. Stachel 1 & Freya M. Mowat 1,3 & Korinn E. Saker 1 & Natasha J. Olby 1 Received: 19 February 2020 / Accepted: 22 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Age is a primary risk factor for multiple comorbidities including neurodegenerative diseases. Pet dogs and humans represent two populations that have experienced a significant increase in average life expectancy over the last century. A higher prevalence of age-related neurodegenerative diseases has been observed across both species, and human diseases, such as Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS), have canine analogs, canine cognitive dysfunction (CCD), and degenerative myelopathy (DM) respectively. In humans, protein biomarkers have proved useful in the prediction and diagnosis of neurodegeneration. Molecular signatures of many proteins are highly conserved across species. In this study, we explored the potential of the neuronal cytoskeletal protein neurofilament light chain (NfL) as a biomarker of neuro-aging in dogs using an ultrasensitive single-molecule array assay to measure plasma concentrations. Healthy dogs of different ages and dogs affected with CCD and DM were evaluated. The mean plasma NfL concentrations in the different age groups of the healthy population were as follows: 4.55 ± 1.70 pg/mL in puppy/junior group (0.43–2 years), 13.51 ± 6.8 pg/mL in adult/mature group (2.1–9 years), and 47.1 ± 12.68 pg/mL in geriatric/senior group (9.3–14.5 years). Concentrations in dogs with DM (7.5–12.6 years) and CCD (11.0– 15.6 years) were 84.17 ± 53.57 pg/mL and 100.73 ± 83.72 pg/mL, respectively. Plasma NfL increases in an age-dependent manner and is significantly elevated in dogs diagnosed with neurodegenerative disease. This work identified plasma NfL as a key clinical index of neuro-aging and neurodegeneration in pet dogs. Our findings mirror recent reports from human neurodegenerative diseases. Keywords Canine . Cognitive dysfunction . Alzheimer’s disease . Amyotrophic lateral sclerosis . Degenerative myelopathy
Introduction Improvements in healthcare, nutrition, and lifestyle have contributed to an increased life expectancy in both dogs Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-01951-0) contains supplementary material, which is available to authorized users. * Natasha J. Olby [email protected] 1
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr., Raleigh, NC 27607, USA
2
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
3
Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA
and humans [1–3]. Unfortunately, extended lifespan has been paralleled by a concurr
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