title: Cerebrospinal Fluid Levels of Phosphorylated Neurofilament Heavy as a Diagnostic Marker of Canine Degenerative Myelopathy.
abstract: BACKGROUND
  No definitive, antemortem diagnostic test for canine degenerative myelopathy (DM) is available. Phosphorylated neurofilament heavy (pNF-H) is a promising biomarker for nervous system diseases.
  
  
  OBJECTIVE
  Cerebrospinal fluid (CSF) and serum pNF-H is a detectable biological marker for diagnosis of canine DM.
  
  
  METHODS
  Fifty-three DM-affected, 27 neurologically normal, 7 asymptomatic at-risk, and 12 DM mimic dogs.
  
  
  METHODS
  Archived CSF and serum pNF-H concentrations were determined by a commercially available ELISA. A receiver-operating characteristic (ROC) curve was generated with CSF values.
  
  
  RESULTS
  Compared with old control dogs, median CSF pNF-H concentration was increased in all stages of DM; old dogs 5.1 ng/mL (interquartile range [IQR] 1.4-9.3) versus DM stage 1 23.9 ng/mL (IQR 20.8-29.6; P < .05) versus DM stage 2 36.8 ng/mL (IQR 22.9-51.2; P < .0001) versus DM stage 3 25.2 ng/mL (IQR 20.2-61.8; P < .001) versus DM stage 4 38.0 ng/mL (IQR 11.6-59.9; P < .01). Degenerative myelopathy stage 1 dogs had increased median CSF pNF-H concentrations compared with asymptomatic, at-risk dogs (3.4 ng/mL [IQR 1.5-10.9; P < .01]) and DM mimics (6.6 ng/mL [IQR 3.0-12.3; P < .01]). CSF pNF-H concentration >20.25 ng/mL was 80.4% sensitive (confidence interval [CI] 66.09-90.64%) and 93.6% specific (CI 78.58-99.21%) for DM. Area under the ROC curve was 0.9467 (CI 0.92-0.9974). No differences in serum pNF-H concentration were found between control and DM-affected dogs.
  
  
  CONCLUSIONS
  pNF-H concentration in CSF is a sensitive biomarker for diagnosis of DM. Although there was high specificity for DM in this cohort, further study should focus on a larger cohort of DM mimics, particularly other central and peripheral axonopathies.
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO.
authors.forename: C M
authors.initials: CM
authors.lastname: Toedebusch
authors.affiliation: Division of Biological Sciences, Bond Life Sciences Center, University of Missouri-Columbia, Columbia, MO.
authors.forename: M D
authors.initials: MD
authors.lastname: Bachrach
authors.affiliation: Division of Biological Sciences, Bond Life Sciences Center, University of Missouri-Columbia, Columbia, MO.
authors.forename: V B
authors.initials: VB
authors.lastname: Garcia
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO.
authors.forename: G C
authors.initials: GC
authors.lastname: Johnson
authors.affiliation: Mason Eye Institute, School of Medicine, University of Missouri-Columbia, Columbia, MO.
authors.forename: M L
authors.initials: ML
authors.lastname: Katz
authors.affiliation: EnCor Biotechnology Inc, Gainesville, FL.
authors.forename: G
authors.initials: G
authors.lastname: Shaw
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO.
authors.forename: J R
authors.initials: JR
authors.lastname: Coates
authors.affiliation: Division of Biological Sciences, Bond Life Sciences Center, University of Missouri-Columbia, Columbia, MO.
authors.forename: M L
authors.initials: ML
authors.lastname: Garcia
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D004283:Dog Diseases / Q000097:blood / Q000134:cerebrospinal fluid*; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D019636:Neurodegenerative Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000662:veterinary*; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D012372:ROC Curve; D013118:Spinal Cord Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000662:veterinary*
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins
keywords: Amyotrophic lateral sclerosis; Biomarker; Dog; Neurodegenerative disease