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Plasma methionine sulfoxide in persons with familial Alzheimer’s disease mutations
Ringman, John M. Fithian, Andrew T. Gylys, Karen Cummings, Jeffrey L. Coppola, Giovanni Elashoff, David Pratico, Domenico Moskovitz, Jackob Bitan, Gal
Ringman, John M.
Fithian, Andrew T.
Gylys, Karen
Cummings, Jeffrey L.
Coppola, Giovanni
Elashoff, David
Pratico, Domenico
Moskovitz, Jackob
Bitan, Gal
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Abstract
BACKGROUND: Convergent evidence suggests that oxidative stress plays a central role in the pathology of Alzheimer’s disease (AD). We asked if consequently, oxidation of methionine residues to methionine sulfoxide (MetO) increased in plasma proteins of persons carrying familial AD (FAD) mutations. METHODS: Plasma was collected from 31 persons from families harboring PSEN1 or APP mutations. Using Western blot analysis with a novel anti-MetO polyclonal antibody, MetO levels were measured and compared between FAD mutation carriers (MCs) and non-mutation carrying (NCs) kin. RESULTS: A MetO-positive 120 kDa gel band distinguished FAD MCs and NCs (mean 11.4 ± 2.8 vs. 4.0 ± 3.1, p = 0.02). In a subset of subjects for whom both measurements were available, MetO levels correlated well with plasma F2-isoprostane (r = 0.81, p < 0.001) and superoxide dismutase 1 (r = 0.52, p = 0.004) levels. CONCLUSIONS: Our data provide evidence for elevated MetO levels in persons carrying FAD mutations that correlate with other indices of oxidative stress and suggest that plasma oxidative stress markers may be useful for diagnosis of AD.
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The final, published version of this article is available at http://www.karger.com/?doi=10.1159/000338546.
Date
2012
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Karger Publishers
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Keywords
Oxidative stress, Isoprostanes, Plasma, Superoxide dismutase, Presenilin-1, Amyloid β-protein precursor
Citation
Ringman, J. M., Fithian, A. T., Gylys, K., Cummings, J. L., Coppola, G., Elashoff, D., … Bitan, G. (2012). Plasma methionine sulfoxide in persons with familial Alzheimer’s disease mutations. Dementia and Geriatric Cognitive Disorders, 33(4), 219–225. http://doi.org/10.1159/000338546