INCREASED OXIDATIVE DAMAGE IN LYMPHOCYTES OF ALZHEIMER'S DISEASE PATIENTS

Abstract

Journal of the American Geriatrics SocietyVolume 45, Issue 12 p. 1536-1537 Free Access INCREASED OXIDATIVE DAMAGE IN LYMPHOCYTES OF ALZHEIMER'S DISEASE PATIENTS First published: 27 April 2015 https://doi.org/10.1111/j.1532-5415.1997.tb03212.xCitations: 2AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat To the Editor: Oxidative stress has been involved in the pathogenesis of several neurodegenerative diseases. Free radicals can damage cellular structures reacting with lipids, proteins, and nucleic acids. 8-hydroxy-2′-deoxyguanosine (8-OHdG) is a reliable marker of oxidative DNA modification. High levels of 8-OHdG were found in lymphocytes or mononuclear cells of subjects suffering from different autoimmune diseases1 or diabetes.2 In a previous study,3 we found a marked increase of nuclear and mitochondrial 8-OHdG in brains of Alzheimer disease (AD) patients compared with normal aged subjects. In order to further evaluate the presence of oxidative damage in AD, we measured 8-OHdG in lymphocytes obtained from 12 AD patients (mean age ± SD 73.3 ± 6.0) and 12 normal controls (mean age ± SD 75.8 ± 6.4). Ten milliliters of heparinized blood was layered on Lymphoprep (Nycomed) and centrifuged at 800 g. Nuclear DNA was extracted from pelleted lymphocytes after osmotic lysis of red blood cells and washing with saline. 8-OHdG was measured by means of HPLC with electrochemical detection as previously reported.3 A significantly higher content of 8-OHdG, expressed as fmol/μg DNA, was found in lymphocytes of AD patients (40.4 ± 12.2; range 24.9-59.8) compared with controls (23.7 ± 7.2; range 14.0 −35.2) (P < .001) (Figure 1). This finding might reflect an imbalance between oxidants and antioxidants4 or a defective DNA repair.5 The high levels of 8-OHdG both in brain tissue and in lymphocytes support the view of AD as a systemic disease whose alterations, although prominent in the central nervous system, also involve other tissues. Therefore, a greater effort in studying peripheral alterations in AD is advisable. Figure 1Open in figure viewerPowerPoint Scattergram of 8-OHdG content, expressed as fmol/μg DNA, in control and AD lymphocytes. REFERENCES 1 Bashir S, Harris G, Denman MA et al. Oxidative damage and cellular sensitivity to oxidative stress in human autoimmune diseases. Ann Rheum Dis 1993; 52: 659– 666. CrossrefCASPubMedWeb of Science®Google Scholar 2 Dandona P, Thusu K, Cook S, et al. Oxidative damage to DNA in diabetes mellitus. Lancet 1996; 347: 444– 445. CrossrefCASPubMedWeb of Science®Google Scholar 3 Mecocci P, MacGarvey U, Beal MF. Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease. Ann Neurol 1994; 36: 747– 751. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 4 Beal MF. Aging, energy and oxidative stress in neurodegenerative diseases. Ann Neurol 1995; 38: 357– 366. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 5 Parshad R, Sanford KK, Price FM et al. Fluorescent light-induced chromatid breaks distinguish Alzheimer disease cells from normal cells in tissue culture. Proc Natl Acad Sci USA 1996; 93: 5146– 5150. CrossrefCASPubMedWeb of Science®Google Scholar Citing Literature Volume45, Issue12December 1997Pages 1536-1537 FiguresReferencesRelatedInformation