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Background  Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is a neurodegenerative disorder affecting genetically predisposed foals maintained on an α‐tocopherol (α‐TOH) deficient diet. Currently no antemortem diagnostic test for eNAD/EDM is available.    Hypothesis  Because α‐TOH deficiency is associated with increased lipid peroxidation, it was hypothesized that F 2 ‐isoprostanes (F 2 IsoP), F 4 ‐neuroprostanes (F 4 NP) and oxysterols derived from free radical oxidation would be increased in the cerebrospinal fluid (CSF) and neural tissue of eNAD/EDM affected horses and could serve as potential biomarkers for disease.    Animals  Isoprostane Study A: 14 Quarter horse foals (10 healthy foals and 4 eNAD/EDM affected foals) at 1 and 6 months of age. Isoprostane Study B: 17 eNAD/EDM affected and 10 unaffected horses ≥ 1‐4 years of age. Oxysterol study: eNAD/EDM affected (n = 14, serum; n = 11, CSF; n = 10, spinal cord [SC]) and unaffected horses 1‐4 years of age (n = 12, serum; n = 10, CSF; n = 7, SC).    Procedures  Cerebrospinal fluid [F 2 IsoP] and [F 4 NP] were assessed using gas chromatography‐negative ion chemical ionization mass spectrometry. Serum, CSF, and cervical SC [oxysterols] were quantified using high performance liquid chromatography mass spectrometry. Results were compared with respective α‐TOH concentrations.    Results  Spinal cord [7‐ketocholesterol], [7‐hydroxycholesterol], and [7‐keto‐27‐hydrocholesterol] were higher in eNAD/EDM horses whereas [24‐ketocholesterol] was lower. No significant difference was found in CSF [F 2 IsoP] and [F 4 NP], serum [oxysterols] and CSF [oxysterols] between eNAD/EDM affected and unaffected horses. No correlation was found between [F 2 IsoP], [F 4 NP], or [oxysterols] and respective [α‐TOH].    Conclusions and Clinical Importance  In the SC, targeted markers of cholesterol oxidation were significantly increased in horses with eNAD/EDM.

Lipid peroxidation biomarkers for evaluating oxidative stress in equine neuroaxonal dystrophy