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Serum elevated gamma glutamyltransferase levels may be a marker for oxidative stress in Alzheimer's disease

Published online by Cambridge University Press:  01 August 2008

Burcu Balam Yavuz*
Affiliation:
Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Geriatric Medicine, Ankara, Turkey
Bunyamin Yavuz
Affiliation:
Kecioren Research Hospital, Department of Cardiology, Ankara, Turkey
Meltem Halil
Affiliation:
Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Geriatric Medicine, Ankara, Turkey
Mustafa Cankurtaran
Affiliation:
Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Geriatric Medicine, Ankara, Turkey
Zekeriya Ulger
Affiliation:
Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Geriatric Medicine, Ankara, Turkey
Eylem Sahin Cankurtaran
Affiliation:
Ankara Oncology Hospital, Department of Psychiatry, Ankara, Turkey.
Kudret Aytemir
Affiliation:
Hacettepe University Faculty of Medicine, Department of Cardiology, Ankara, Turkey
Servet Ariogul
Affiliation:
Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Geriatric Medicine, Ankara, Turkey
*
Correspondence should be addressed to: Dr. Burcu Balam Yavuz, Hacettepe University, Faculty of Medicine, Department of Internal Medicine, Division of Geriatric Medicine, Sihhiye, 06100, Ankara, Turkey. Phone: +903123053071; Fax: +903123051538. Email: bbyavuz@hacettepe.edu.tr.
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Abstract

Background: Gamma glutamyltransferase (GGT) plays a role in cellular glutathione uptake, which is an important element of antioxidant mechanisms. An increase in serum GGT is thought to be an early and sensitive marker of oxidative stress. Oxidative stress has a role in the pathogenesis of Alzheimer's disease (AD). The aim of this study was to investigate the GGT levels in AD.

Method: In this cross-sectional study, 132 patients with AD (mean age: 74.1 ± 7.4, female 62.9%) and 158 age- and gender-matched normal controls (mean age: 74.5 ± 6.3, female 67.1%) were evaluated. For cognitive assessment, MMSE and clock drawing tests were performed; DSM-IV and NINCDS-ADRDA criteria were used. Serum GGT, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase concentrations were determined.

Results: Median (min-max) GGT levels were 18 (9–70) in AD group and 17 (5–32) in normal controls. Mann-Whitney U test showed that GGT levels were significantly higher in AD patients (p = 0.012). Linear regression analysis revealed AD was an independent correlate of elevated GGT levels. Hypertension, diabetes mellitus, total cholesterol, and low density lipoprotein cholesterol were not associated with GGT levels.

Conclusion: GGT levels were increased significantly in AD patients. To evaluate the role of GGT as a marker of oxidative stress in AD, further studies are needed.

Type
Research Article
Copyright
© International Psychogeriatric Association 2008

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References

American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders. 4th edn. Washington, D.C.: American Psychiatric Association.Google Scholar
Betro, M. G., Oon, R. C. and Edwards, J. B. (1973). Gamma-glutamyl transpeptidase and other liver function tests in myocardial infarction and heart failure. American Journal of Clinical Pathology, 60, 679683.Google Scholar
Bourdel-Marchasson, I. et al. (2001). Antioxidant defences and oxidative stress markers in erythrocytes and plasma from normally nourished elderly Alzheimer patients. Age and Ageing, 30, 235241.CrossRefGoogle ScholarPubMed
Buee, L., Hof, P. R. and Delacourte, A. (1997). Brain microvascular changes in Alzheimer's disease and other dementias. Annals of the New York Academy of Sciences, 26, 724.Google Scholar
Daeppen, J. B., Smith, T. L. and Schuckit, M. A. (1998). Influence of age and body mass index on gamma-glutamyltransferase activity: a 15-year followup evaluation in a community sample. Alcoholism, Clinical and Experimental Research, 22, 941944.Google Scholar
de la Torre, J. C. (2002). Vascular basis of Alzheimer's pathogenesis. Annals of the New York Academy of Sciences, 977, 196215.CrossRefGoogle ScholarPubMed
Dede, D. S. et al. (2007). Assessment of endothelial function in Alzheimer's disease: is Alzheimer's disease a vascular disease? Journal of the American Geriatrics Society, 55, 16131617.Google Scholar
Emdin, M. et al. (2001). Prognostic value of serum gamma-glutamyl transferase activity after myocardial infarction. European Heart Journal, 22, 18021807.Google Scholar
Folstein, M. F., Folstein, J. E. and McHugh, P. R. (1975). “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189198.CrossRefGoogle ScholarPubMed
Hughes, C. P. et al. (1982). A new clinical scale scale for the staging of dementia. British Journal of Psychiatry, 140, 566572.CrossRefGoogle ScholarPubMed
Jousilahti, P., Rastenyte, D. and Tuomilehto, J. (2000). Serum gamma-glutamyltransferase, self-reported alcohol drinking, and the risk of stroke. Stroke 31, 18511855.Google Scholar
Karp, D. R., Shimooku, K. and Lipsky, P. E. (2001). Expression of gamma-glutamyl transpeptidase protects ramos B cells from oxidation-induced cell death. The Journal of Biological Chemistry 276, 37983804.CrossRefGoogle Scholar
Kim, D. J. et al. (2005). Serum gamma-glutamyltransferase within its normal concentration range is related to the presence of diabetes and cardiovascular risk factors. Diabetic Medicine, 22, 11341140.CrossRefGoogle Scholar
Kugelman, A. et al. (1994). Gamma-Glutamyl transpeptidase is increased by oxidative stress in rat alveolar L2 epithelial cells. American Journal of Respiratory Cell and Molecular Biology 11, 58655892.Google Scholar
Launer, L. (2002). Demonstrating the case that Alzheimer disease is a vascular disease; epidemiologic evidence. Ageing Research Reviews, 1, 6167.CrossRefGoogle ScholarPubMed
Launer, L. J. et al. (2000). Midlife blood pressure and dementia. Honolulu aging study. Neurobiology of Aging, 21, 4955.CrossRefGoogle ScholarPubMed
Lee, D. H., Blomhoff, R. and Jacobs Jr, D. R. (2004). Is serum gamma glutamyltransferase a marker of oxidative stress? Free Radical Research, 38, 535539.Google Scholar
Libby, P. (2002). Inflammation in atherosclerosis. Nature, 420, 868–74.Google Scholar
Lim, J. S. et al. (2004). Is serum gamma-glutamyl transferase inversely associated with serum antioxidants as a marker of oxidative stress? Free Radical Biology and Medicine, 37, 10181023.Google Scholar
McKhann, G. et al. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology, 34, 939944.Google Scholar
Nakanishi, N., Suzuki, K. and Tatara, K. (2004). Serum gamma-glutamyl transferase and risk of metabolic syndrome and type 2 diabetes in middle-aged Japanese men. Diabetes Care 27, 14271432.CrossRefGoogle ScholarPubMed
Nilssen, O. and Førde, O. H. (1994). Seven-year longitudinal population study of change in gamma-glutamyltransferase: the Tromsø Study. American Journal of Epidemiology, 139, 787792.CrossRefGoogle ScholarPubMed
Nilssen, O., Førde, O. H. and Bren, T. (1990). The Tromsø study – distribution and population determinants of gamma-glutamyltransferase. American Journal of Epidemiology, 132, 318326.CrossRefGoogle ScholarPubMed
Onat, A. et al. (2006). Serum gamma glutamyltransferase as a marker of metabolic syndrome and coronary disease likelihood in nondiabetic middle-aged and elderly adults. Preventive Medicine, 43, 136139.Google Scholar
Pansari, K., Gupta, A. and Thomas, P. (2002). Alzheimer's disease and vascular factors: facts and theories. International Journal of Clinical Psychiatry, 56, 197203.Google ScholarPubMed
Paolicchi, A. et al. (2006). β-Lipoprotein- and LDL-associated serum gamma-glutamyltransferase in patients with coronary atherosclerosis. Atherosclerosis, 186, 8085.CrossRefGoogle ScholarPubMed
Petersen, R. C. et al. (1999). Mild cognitive impairment: clinical characterization and outcome. Archives of Neurology, 56, 303308.CrossRefGoogle ScholarPubMed
Reitz, C. et al. (2004). Relation between plasma lipids to Alzheimer's disease and vascular dementia. Archives of Neurology, 61, 705714.CrossRefGoogle Scholar
Rinaldi, P. et al. (2003). Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer's disease. Neurobiology of Aging, 24, 915919.CrossRefGoogle ScholarPubMed
Rottkamp, C. A. et al. (2000). Oxidative stress, antioxidants, and Alzheimer disease. Alzheimer Disease and Associated Disorders, 14 (Suppl. 1), S62S66.CrossRefGoogle ScholarPubMed
Sano, M. et al. (1997). A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. The New England Journal of Medicine, 336, 12161222.Google Scholar
Seshadri, S. (2002). Plasma homosistein as a risk factor for dementia and Alzheimer disease. The New England Journal of Medicine, 346, 476483.CrossRefGoogle Scholar
Stahelin, H. B., Monsch, A. U. and Spiegel, R. (1997). Early diagnosis of dementia via a two-step screening and diagnostic procedure. International Psychogeriatrics, 9, 123130.Google Scholar
Stocker, R. and Keaney Jr, J. F. (2004). Role of oxidative modifications in atherosclerosis. Physiological Reviews, 84, 1381–478.Google Scholar
Takahashi, Y. et al. (1997). Nitrogen dioxide exposure activates gamma-glutamyl transferase gene expression in rat lung. Toxicology and Applied Pharmacology, 143, 388396.Google Scholar
Wannamethee, G., Ebrahim, S. and Shaper, A. G. (1995). Gamma glutamyltransferase: determinants and association with mortality from ischemic heart disease and all causes. American Journal of Epidemiology, 142, 699708.CrossRefGoogle ScholarPubMed
Yamada, J. et al. (2006). Elevated serum levels of alanine aminotransferase and gamma glutamyltransferase are markers of inflammation and oxidative stress independent of the metabolic syndrome. Atherosclerosis, 89, 198205.CrossRefGoogle Scholar
Zhu, X. et al. (2004). Oxidative stress signalling in Alzheimer's disease. Brain Research, 1000, 3239.Google Scholar
Zhu, X. et al. (2005). Oxidative imbalance in Alzheimer's disease. Molecular Neurobiology, 31, 205217.CrossRefGoogle ScholarPubMed
Zhu, X. et al. (2007). Vascular oxidative stress in Alzheimer disease. Journal of the Neurological Sciences, 257, 240246.Google Scholar
Zulli, R. et al. (2005). QT dispersion and heart rate variability abnormalities in Alzheimer's disease and in mild cognitive impairment. Journal of the American Geriatrics Society, 53, 21352139.CrossRefGoogle ScholarPubMed