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Protein glycation, oxidation and nitration adduct residues and free adducts of cerebrospinal fluid in Alzheimer's disease and link to cognitive impairment

  1. Naila Ahmed,
  2. Usman Ahmed,
  3. Paul J. Thornalley,
  4. Klaus Hager,
  5. Gerd Fleischer,
  6. Gerald Münch

Article first published online: 14 DEC 2004

DOI: 10.1111/j.1471-4159.2004.02864.x

Issue

Journal of Neurochemistry

Journal of Neurochemistry

Volume 92, Issue 2, pages 255–263, January 2005

Additional Information

How to Cite

Ahmed, N., Ahmed, U., Thornalley, P. J., Hager, K., Fleischer, G. and Münch, G. (2005), Protein glycation, oxidation and nitration adduct residues and free adducts of cerebrospinal fluid in Alzheimer's disease and link to cognitive impairment. Journal of Neurochemistry, 92: 255–263. doi: 10.1111/j.1471-4159.2004.02864.x

Author Information

  1. *Department of Biological Sciences, University of Essex, Colchester, Essex, UK †Klinik für Medizinische Rehabilitation und Geriatrie der Henriettenstiftung, Hannover, Germany ‡Neuroimmunological Cell Biology Unit, Interdisciplinary Center for Clinical Research (IZKF), University of Leipzig, Leipzig, Germany §Comparative Genomic Center, James Cook University, Townsville, Australia

*Address correspondence and reprint requests to Dr Paul J. Thornalley, Department of Biological Sciences, University of Essex, Central Campus, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK. E-mail: thorp@essex.ac.uk

Publication History

  1. Issue published online: 14 DEC 2004
  2. Article first published online: 14 DEC 2004
  3. Received April 26, 2004; revised manuscript received August 2, 2004; accepted August 24, 2004.

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Keywords:

  • Alzheimer's disease;
  • cerebrospinal fluid;
  • glycation;
  • methylglyoxal;
  • nitrotyrosine;
  • oxidative stress

Abstract

Increased damage to proteins by glycation, oxidation and nitration has been implicated in neuronal cell death leading to Alzheimer's disease (AD). Protein glycation, oxidation and nitration adducts are consequently formed. Quantitative screening of these adducts in CSF may provide a biochemical indicator for the diagnosis of AD. To assess this, we measured 11 glycation adducts, three oxidation adducts and a nitration adduct, determining both protein adduct residues and free adducts, in CSF samples of age-matched normal healthy subjects (n = 18) and subjects with Alzheimer's disease (n = 32). In CSF protein, the concentrations of 3-nitrotyrosine, Nɛ-carboxymethyl-lysine, 3-deoxyglucosone-derived hydroimidazolone and N-formylkynurenine residues were increased in subjects with Alzheimer's disease. In CSF ultrafiltrate, the concentrations of 3-nitrotyrosine, methylglyoxal-derived hydroimidazolone and glyoxal-derived hydroimidazolone free adducts were also increased. The Mini-Mental State Examination (MMSE) score correlated negatively with 3-nitrotyrosine residue concentration (p < 0.05), and the negative correlation with fructosyl-lysine residues just failed to reach significance (p = 0.052). Multiple linear regression gave a regression model of the MMSE score on 3-nitrotyrosine, fructosyl-lysine and Nɛ-carboxyethyl-lysine residues with p-values of 0.021, 0.031 and 0.052, respectively. These findings indicate that protein glycation, oxidation and nitration adduct residues and free adducts were increased in the CSF of subjects with Alzheimer's disease. A combination of nitration and glycation adduct estimates of CSF may provide an indicator for the diagnosis of Alzheimer's disease.

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