title: Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber hereditary optic neuropathy (LHON).
abstract: OBJECTIVE
  To determine the profile of neurodegeneration in Leber hereditary optic neuropathy (LHON).
  
  
  METHODS
  We quantitated serum levels of phosphorylated neurofilament heavy chain (pNF-H) in a Brazilian pedigree of 16 affected patients and 59 carriers with LHON, both molecularly characterized as harboring the G to A mutation at nucleotide 11,778 of the mitochondrial genome. The association of subject characteristics to pNF-H levels was studied with multiple regression; pNF-H data were square-root transformed to effect normality of distribution of residuals. Relationships between the square-root of pNF-H and age and sex were investigated within groups with Pearson correlation and the two-sample t-test. Linear regression was used to assess the difference between groups and to determine if the relationship of age was different between affected individuals and carriers. Results of plotting pNF-H levels by age suggested a nonlinear, quadratic association so age squared was used in the statistical analysis. ANCOVA was used to assess the influence of age and group on pNF-H levels.
  
  
  RESULTS
  In the carrier group, there was a significant correlation of square-root pNF-H (mean=0.24 ng/ml(2)) with age (r=0.30, p=0.022) and a stronger correlation with quadratic age (r=0.37, p=0.003). With a higher mean pNF-H (0.33 ng/ml(2)) for the affected group, correlations were of similar magnitude, although they were not statistically significant: age (r=0.22, p=0.42), quadratic age (r=0.22, p=0.45). There was no correlation between age and pNF-H levels (mean=0.34 ng/ml(2)) in the off-pedigree group: age (r=0.03, p=0.87), quadratic age (r=0.04, p=0.84). There was no difference between sexes and pNF-H levels in any of the groups (affected, p=0.65; carriers, p=0.19; off-pedigree, p=0.93).
  
  
  CONCLUSIONS
  Elevated pNF-H released into the serum of some affected LHON patients may suggest that axonal degeneration occurs at some point after loss of visual function. Increases in pNF-H levels of carriers with increasing age, not seen in off-pedigree controls, may suggest subtle subclinical optic nerve degeneration.
authors.affiliation: Bascom Palmer Eye Institute, McKnight Vision Research Center, Miami, FL 33136, USA. jguy@med.miami.edu
authors.forename: John
authors.initials: J
authors.lastname: Guy
authors.forename: Gerry
authors.initials: G
authors.lastname: Shaw
authors.forename: Fred N
authors.initials: FN
authors.lastname: Ross-Cisneros
authors.forename: Peter
authors.initials: P
authors.lastname: Quiros
authors.forename: Solange R
authors.initials: SR
authors.lastname: Salomao
authors.forename: Adriana
authors.initials: A
authors.lastname: Berezovsky
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.forename: William J
authors.initials: WJ
authors.lastname: Feuer
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Sadun
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002645:Chickens; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000150:complications* / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism*; D029242:Optic Atrophy, Hereditary, Leber / Q000150:complications* / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D017186:Titrimetry
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins; D010750:Phosphoproteins; C051774:neurofilament protein H