Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber Hereditary Optic Neuropathy (LHON)

John Guy, Gerry Shaw, Fred N. Ross-Cisneros, Peter Quiros, Solange R. Salomao, Adriana Berezovsky, Valerio Carelli, William J. Feuer, Alfredo A. Sadun

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Abstract

Purpose: 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/ml2) 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/ml2) 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/ml2) 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.

Original languageEnglish
Pages (from-to)2443-2450
Number of pages8
JournalMolecular Vision
Volume14
Publication statusPublished - Dec 22 2008

ASJC Scopus subject areas

  • Ophthalmology

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    Guy, J., Shaw, G., Ross-Cisneros, F. N., Quiros, P., Salomao, S. R., Berezovsky, A., Carelli, V., Feuer, W. J., & Sadun, A. A. (2008). Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber Hereditary Optic Neuropathy (LHON). Molecular Vision, 14, 2443-2450.