Increased Expression but Reduced Activity of Antioxidant Enzymes in Alzheimer's Disease (original) (raw)

Article type: Research Article

Affiliations: [a] Department of Pathology, University of Louisville - Veterans Affairs Medical Center, Louisville, KY, USA | [b] Departments of Pathology and Neurology, University of South Alabama, Mobile, AL, USA | [c] Department of Psychiatry, University of North Texas Health Science Center, Fort Worth, Texas, USA | [d] Fishberg Center for Neurobiology and Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA

Correspondence: [*] Corresponding author: Miguel A. Pappolla, M.D., University of South Alabama, College of Medicine, Mobile, Alabama 36617, USA, Tel.: +1 334 4717804; Fax: +1 334 4717838; E-mail: [email protected].

Abstract: A growing body of data suggests that free radicals are involved in the pathogenesis of Alzheimer's disease (AD). Increased expression of antioxidant enzymes, such as superoxide dismutase (SOD), and their co-localization to senile plaques and dystrophic neurites have established a firm association between free-radical mediated injury and the disease neuropathology. While several studies have confirmed these findings, there is conflicting information regarding the activity of some of the enzymes. In the current report, we assayed the activity of superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) from the same areas of the tissue showing increased expression of SOD1 and SOD2 (parallel sequential slices). Nine brains with neuropathologically confirmed AD and six neuropathologically normal, age-matched, controls were examined. Despite marked increased expression of SOD1 and SOD2 within senile plaques in all the cases studied, the activities of SOD, GSH-Px and catalase were significantly lower in AD than in control brains. The difference was most profound in the case of catalase followed by GSH-Px and SOD. These data are in qualitative agreement with that of several laboratories, and support a decrease rather than an increase, in antioxidant enzyme activity. The findings suggest two main possibilities. On one hand, the observed reduced activity along with antigenically increased expression may be consistent with inactivation of excess protein that has been synthesized under conditions of high oxidative stress. Increased protein oxidation coupled with enzyme inactivation is a documented, aging-associated phenomenon. Alternatively, the increased immuno-reactivity may reflect a redistribution phenomenon as the enzymes become more concentrated at the sites of increased oxidative stress, despite an over all reduction in their activity.

Keywords: Alzheimer's disease, superoxide dismutase, amyloid beta protein, oxidative stress, senile plaques, Aβ, oxidation, antioxidant enzymes

DOI: 10.3233/JAD-1999-1301

Journal: Journal of Alzheimer's Disease, vol. 1, no. 3, pp. 139-145, 1999