title: Increased lipid peroxidation in sera of ALS patients: a potential biomarker of disease burden.
abstract: BACKGROUND
  Markers of oxidative stress and immune activation are significantly elevated in postmortem ALS CNS tissue, although the relevance to pathogenesis is unclear.
  
  
  OBJECTIVE
  To determine the degree and distribution of oxidative stress and immune activation in living ALS patients and whether these levels correlate with the rate of progression or extent of disease.
  
  
  METHODS
  Serum and CSF samples from sporadic ALS (sALS) patients were assayed for 4-hydroxy-2,3-nonenal (HNE), a lipid peroxidation product, and monocyte chemoattractant protein-1alpha (MCP-1alpha), a beta-chemokine, by high-performance liquid chromatography and ELISA and compared with levels measured in disease and normal control subjects by one-way analysis of variance. SALS serum levels were analyzed in relation to rate of progression, stage of disease, and drug therapy.
  
  
  RESULTS
  HNE levels were significantly elevated in the sera and spinal fluid of sALS patients compared with control populations and positively correlated with extent of disease but not rate of progression. MCP-1alpha levels were also elevated in the sera of sALS patients, with the exception of the neurodegenerative disease control subjects, but decreased with advancing disease. CSF MCP-1alpha levels were not different between the sampled populations. There was no correlation between serum HNE and MCP-1alpha levels in sALS patients and extent of disease. However, an inverse relationship between HNE and MCP-1alpha was demonstrable in vitro. Low levels of HNE stimulated release of MCP-1alpha from cultured human macrophages, whereas high levels inhibited release of MCP-1alpha.
  
  
  CONCLUSIONS
  These data confirm the presence of increased oxidative stress and immune activation in ALS patients. HNE is also suggested as a possible biomarker of disease.
authors.affiliation: Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: E P
authors.initials: EP
authors.lastname: Simpson
authors.forename: Y K
authors.initials: YK
authors.lastname: Henry
authors.forename: J S
authors.initials: JS
authors.lastname: Henkel
authors.forename: R G
authors.initials: RG
authors.lastname: Smith
authors.forename: S H
authors.initials: SH
authors.lastname: Appel
mesh_terms: D000328:Adult; D000368:Aged; D000447:Aldehydes / Q000097:blood* / Q000134:cerebrospinal fluid; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid / Q000276:immunology; D015415:Biomarkers; D018932:Chemokine CCL2 / Q000097:blood* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000097:blood / Q000134:cerebrospinal fluid; D018384:Oxidative Stress
chemical_list: D000447:Aldehydes; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C027576:4-hydroxy-2-nonenal