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Home / Equine Research Bank / Equine Vet J / Serum and cerebrospinal fluid phosphorylated neurofilament h...
Equine veterinary journal2021; 54(2); 290-298; doi: 10.1111/evj.13452

Serum and cerebrospinal fluid phosphorylated neurofilament heavy protein concentrations in equine neurodegenerative diseases.

Abstract: Currently, there is little information regarding the concentrations of phosphorylated neurofilament heavy protein (pNfH) in the serum and cerebrospinal fluid (CSF) of horses with neurodegenerative diseases. Specifically, pNfH concentrations have not yet been evaluated in horses with equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM). Objective: To determine pNfH concentrations using a commercial enzyme-linked immunosorbent assay (ELISA) in serum and CSF from control horses and horses with eNAD/EDM, cervical vertebral compressive myelopathy (CVCM) and Shivers. Methods: Case-control study using biobanked samples from diseased horses and prospective or biobanked samples from control horses. Methods: The pNfH ELISA was performed on samples from horses diagnosed with eNAD/EDM (n = 64), CVCM (n = 26) and Shivers (n = 9) and 51 neurologically normal control horses. Results: Median and 95% confidence interval (CI) serum pNfH concentrations in control, CVCM, and eNAD/EDM horses were 0.08 ng/mL (0.07-0.15), 0.07 ng/mL (0.07-0.15) and 0.07 ng/mL (0.07-1.13), respectively. Serum pNfH concentrations were below the limit of detection (<0.07 ng/mL) for all Shivers horses. CSF pNfH concentrations in control, CVCM-, eNAD/EDM- and Shivers-affected horses were 1.26 ng/mL (1.06-1.5), 3.07 ng/mL (1.15-29.9), 1.78 ng/mL (1.5-2.28) and 1.39 ng/mL (0.74-3.89), respectively. CSF pNfH concentrations were significantly higher in CVCM (P = .001) and eNAD/EDM (P  = .01) affected horses compared to control horses. Serum pNfH concentrations >1 ng/mL were significantly associated with eNAD/EDM (P = .01) with only 12% sensitivity but 99% specificity. CSF pNfH concentrations >3 ng/mL were significantly associated with CVCM (P = .0002), with 50% sensitivity and 86% specificity. Conclusions: A limited number of control horses tested were <1 year of age. Conclusions: Serum pNfH concentrations are specifically increased (>1 ng/mL) in some horses with eNAD/EDM. Increased CSF pNfH concentrations (>3 ng/mL) can be observed with eNAD/EDM or CVCM.
© 2021 EVJ Ltd.
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Publication Date: 2021-05-09 PubMed ID: 33969539DOI: 10.1111/evj.13452Google Scholar: Lookup
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Summary

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This study investigates the concentrations of phosphorylated neurofilament heavy protein (pNfH) in the serum and cerebrospinal fluid of horses with neurodegenerative diseases. The study specifically focus on equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM), cervical vertebral compressive myeloencephalopathy (CVCM), and Shivers and reveals that serum pNfH concentrations increase in some horses with eNAD/EDM and increased CSF pNfH concentrations can be observed with eNAD/EDM or CVCM.

Research Methodology

  • The study utilizes a case-control setup with biobanked samples from horses diagnosed with eNAD/EDM, CVCM, and Shivers. The control group consisted of biobanked samples from neurologically normal horses.
  • To determine pNfH concentrations, a commercial enzyme-linked immunosorbent assay (ELISA) was performed on the serum and CSF samples from the horses.

Findings

  • Findings revealed that serum pNfH concentrations for control, CVCM, and eNAD/EDM horses were relatively similar, with all Shivers horses reporting serum pNfH concentrations below the limit of detection.
  • However, CSF pNfH concentrations showed variability. Horses affected by CVCM and eNAD/EDM had significantly higher CSF pNfH concentrations than control horses.
  • Serum pNfH concentrations greater than 1 ng/mL were significantly correlated with eNAD/EDM, although this was only true with a sensitivity of 12%.
  • CSF pNfH concentrations higher than 3 ng/mL were significantly associated with CVCM with a sensitivity of 50%.

Conclusions

  • The research suggests that serum pNfH concentrations specifically increase in some horses diagnosed with eNAD/EDM.
  • Horses diagnosed with either eNAD/EDM or CVCM show increased CSF pNfH concentrations, indicating that this metric could potentially be useful for diagnosing these specific conditions.
  • However, the researchers do note some limitations, including a limited number of control horses that were tested and under a year old, which may have affected results.

Cite This Article

APA
Edwards LA, Donnelly CG, Reed SM, Valberg S, Chigerwe M, Johnson AL, Finno CJ. (2021). Serum and cerebrospinal fluid phosphorylated neurofilament heavy protein concentrations in equine neurodegenerative diseases. Equine Vet J, 54(2), 290-298. https://doi.org/10.1111/evj.13452

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 54
Issue: 2
Pages: 290-298

Researcher Affiliations

Edwards, Lisa A
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Donnelly, Callum G
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Reed, Stephen M
  • Rood and Riddle Equine Hospital, Lexington, KY, USA.
Valberg, Stephanie
  • Department of Large Animal Clinical Sciences, Mary Anne McPhail Equine Performance Center, Michigan State University, East Lansing, MI, USA.
Chigerwe, Munashe
  • Department of Veterinary Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.
Johnson, Amy L
  • Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, USA.
Finno, Carrie J
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.

MeSH Terms

  • Animals
  • Case-Control Studies
  • Horse Diseases
  • Horses
  • Intermediate Filaments
  • Neuroaxonal Dystrophies / veterinary
  • Neurodegenerative Diseases / veterinary
  • Neurofilament Proteins / blood
  • Neurofilament Proteins / cerebrospinal fluid
  • Phosphorylation
  • Prospective Studies

Grant Funding

  • 19-01 / UC Davis Center for Equine Health
  • L40 TR001136 / NCATS NIH HHS
  • K01OD015134 / ORIP NIH HHS

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Citations

This article has been cited 7 times.
  1. Bacon EK, Donnelly CG, Bellone RR, Haase B, Finno CJ, Velie BD. Preliminary investigation of potential links between pigmentation variants and opioid analgesic effectiveness in horses during cerebrospinal fluid centesis. BMC Vet Res 2024 Jul 12;20(1):311.
    doi: 10.1186/s12917-024-04139-zpubmed: 38997753google scholar: lookup
  2. Palmisano M, Kulp J, Bender S, Stefanovski D, Robinson M, Johnson A. Measurement of 8-hydroxy-2'-deoxyguanosine in serum and cerebrospinal fluid of horses with neuroaxonal degeneration and other causes of proprioceptive ataxia. J Vet Intern Med 2024 Mar-Apr;38(2):1207-1213.
    doi: 10.1111/jvim.16988pubmed: 38205913google scholar: lookup
  3. Brown KA, Bender SJ, Johnson AL. Clinical and histopathological features in horses with neuroaxonal degeneration: 100 cases (2017-2021). J Vet Intern Med 2024 Jan-Feb;38(1):431-439.
    doi: 10.1111/jvim.16969pubmed: 38095342google scholar: lookup
  4. Ma Y, Peng S, Donnelly CG, Ghosh S, Miller AD, Woolard K, Finno CJ. Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophy. J Vet Intern Med 2024 Jan-Feb;38(1):417-423.
    doi: 10.1111/jvim.16924pubmed: 37937700google scholar: lookup
  5. Donnelly CG, Johnson AL, Reed S, Finno CJ. Cerebrospinal fluid and serum proteomic profiles accurately distinguish neuroaxonal dystrophy from cervical vertebral compressive myelopathy in horses. J Vet Intern Med 2023 Mar;37(2):689-696.
    doi: 10.1111/jvim.16660pubmed: 36929645google scholar: lookup
  6. Yuan A, Nixon RA. Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies. Front Neurosci 2021;15:689938.
    doi: 10.3389/fnins.2021.689938pubmed: 34646114google scholar: lookup
  7. Hales EN, Habib H, Favro G, Katzman S, Sakai RR, Marquardt S, Bordbari MH, Ming-Whitfield B, Peterson J, Dahlgren AR, Rivas V, Ramirez CA, Peng S, Donnelly CG, Dizmang BS, Kallenberg A, Grahn R, Miller AD, Woolard K, Moeller B, Puschner B, Finno CJ. Increased α-tocopherol metabolism in horses with equine neuroaxonal dystrophy. J Vet Intern Med 2021 Sep;35(5):2473-2485.
    doi: 10.1111/jvim.16233pubmed: 34331715google scholar: lookup
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