Peripheral Oxidative Stress Biomarkers in Mild Cognitive Impairment and Alzheimer's Disease

Article type: Research Article

Authors: Torres, Larissa Lobo^a | Quaglio, Nathalia Barbosa^a | de Souza, Gisele Tavares^a | Garcia, Raphael Tamborelli^a | Dati, Lívia Mendonça Munhoz^a | Moreira, Wallace Luiz^a | de Melo Loureiro, Ana Paula^a | de souza-Talarico, Juliana Nery^{b; d} | Smid, Jerusa^b | Porto, Cláudia Selito^b | de Campos Bottino, Cássio Machado^c | Nitrini, Ricardo^b | de Moraes Barros, Silvia Berlanga^a | Camarini, Rosana^e | Marcourakis, Tania^{a; *}

Affiliations: [a] Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil | [b] Behavioral and Cognitive Neurology Unit of the Department of Neurology, University of São Paulo, São Paulo, Brazil | [c] Department of Psychiatry, School of Medicine, University of São Paulo, São Paulo, Brazil | [d] Department of Medical-Surgical Nursing, School of Nursing, University of São Paulo, São Paulo, Brazil | [e] Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil

Correspondence: [*] Correspondence to: T. Marcourakis, Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, Av Prof Lineu Prestes, 580 Bl 13B, CEP-05508-900, São Paulo-SP, Brazil. Tel./Fax: +55 11 3091 2194; E-mail: [email protected].

Abstract: Oxidative stress has been associated with normal aging and Alzheimer's disease (AD). However, little is known about oxidative stress in mild cognitive impairment (MCI) patients who present a high risk for developing AD. The aim of this study was to investigate plasma production of the lipid peroxidation marker, malonaldehyde (MDA) and to determine, in erythrocytes, the enzymatic antioxidant activity of catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) in 33 individuals with MCI, 29 with mild probable AD and 26 healthy aged subjects. GR/GPx activity ratio was calculated to better assess antioxidant defenses. The relationship between oxidative stress and cognitive performance was also evaluated by the Mini Mental State Examination (MMSE). AD patients showed higher MDA levels than both MCI and healthy elderly subjects. MCI subjects also exhibited higher MDA levels compared to controls. Catalase and GPx activity were similar in MCI and healthy individuals but higher in AD. GR activity was lower in MCI and AD patients than in healthy aged subjects. Additionally, GR/GPx ratio was higher in healthy aged subjects, intermediate in MCI and lower in AD patients. No differences in GST activity were detected among the groups. MMSE was negatively associated with MDA levels (r = −0.31, p = 0.028) and positively correlated with GR/GPx ratio in AD patients (r = 0.68, p < 0.001). MDA levels were also negatively correlated to GR/GPx ratio (r = −0.31, p = 0.029) in the AD group. These results suggest that high lipid peroxidation and decreased antioxidant defenses may be present early in cognitive disorders.

Keywords: Aging, Alzheimer's disease, antioxidant enzymes, malonaldehyde, mild cognitive impairment, oxidative stress

DOI: 10.3233/JAD-2011-110284

Journal: Journal of Alzheimer's Disease, vol. 26, no. 1, pp. 59-68, 2011