Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber hereditary optic neuropathy (LHON)

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2008-12-22
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Guy, John
Shaw, Gerry
Ross-Cisneros, Fred N.
Quiros, Peter
Salomão, Solange Rios [UNIFESP]
Berezovsky, Adriana [UNIFESP]
Carelli, Valerio
Feuer, William J.
Sadun, Alfredo Arrigo
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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/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/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/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.
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Molecular Vision. Atlanta: Molecular Vision, v. 14, n. 281, p. 2443-2450, 2008.
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