Increased Protein and Lipid Oxidative Damage in Mitochondria Isolated from Lymphocytes from Patients with Alzheimer's Disease: Insights into the Role of Oxidative Stress in Alzheimer's Disease and Initial Investigations into a Potential Biomarker for this Dementing Disorder
Affiliations: [a] Department of Chemistry, Centre of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA | [b] Department of Clinical and Experimental Medicine, Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy
Correspondence:
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Correspondence to: Professor D. Allan Butterfield, Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA. Tel.: +1 859 257 3184; Fax: +1 859 257 5876; E-mail: dabcns@uky.edu.
Abstract: Alzheimer's disease (AD) is histopathologically characterized by the presence of senile plaques, neurofibrillary tangles, and synapse loss. The main component of senile plaques is amyloid β-peptide (Aβ), which has been shown to induce oxidative stress in in vitro and in vivo studies. AD is associated with elevated levels of oxidative damage in brain and peripheral lymphocytes. Further Aβ has been found to be accumulated in mitochondria, which might contribute to the reported alterations in the mitochondrial morphology, and impaired mitochondrial energy metabolism in AD brain. Biomarkers are desperately needed for earlier diagnosis of AD and to monitor efficacy of new therapies. Hence, in the present study we show that markers of oxidative damage are elevated in mitochondria isolated from AD lymphocytes suggesting that these oxidative stress indices potentially could serve as a viable biomarker for AD.
Keywords: Alzheimer's disease, lymphocytes, mitochondria, 3-nitrotyrosine, oxidative stress, protein-bound 4 hydroxy-2 trans nonenal, protein carbonyls
