Lymphocyte mitochondria: toward identification of peripheral biomarkers in the progression of Alzheimer disease |
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| Institution: | 1. Department of Chemistry, Center of Membrane Sciences, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA;2. Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy;3. Department of Nephrology and Proteomics Center, University of Louisville, Louisville, KY 40292, USA;1. Department of Abdominal and General Surgery, University Clinical Centre Maribor, Maribor, Slovenia;2. Institute of Pathophysiology, Medical School Ljubljana, Ljubljana, Slovenia;3. Department of Laboratory Diagnostics, Clinical Centre Maribor, Maribor, Slovenia;4. Department of Pathology, University Clinical Centre Maribor, Maribor, Slovenia;1. School of Biological Sciences and The Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, 3a Symonds St, Auckland Central 1010, New Zealand;2. Department of Neurosurgery, Marburg University, University Hospital, Baldingerstr., 35053 Marburg, Germany;3. School of Chemical Sciences, The University of Auckland, 23 Symonds St, Auckland 1010, New Zealand;1. Institute of Life Sciences, Scuola Superiore Sant''Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy;2. National Research Council – Institute of Biophysics, Section of Pisa, Via Moruzzi, 1, 56124 Pisa, Italy;1. Department of addictive behaviour and addiction medicine, central institute of mental health, Mannheim, university of Heidelberg, Mannheim, Germany;2. Department of psychiatry and psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany;3. Department of biostatistics, central institute of mental health, Mannheim, university of Heidelberg, Mannheim, Germany;1. Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany;2. Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany;3. Department of Psychiatry and Psychotherapy, Charité, University Medicine, Campus Mitte, Berlin, Germany;4. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University Heidelberg, Mannheim, Germany;5. Institute of Human Genetics, University of Bonn, Bonn, Germany |
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| Abstract: | Alzheimer disease (AD) is an age-related neurodegenerative condition. AD is histopathologically characterized by the presence of three main hallmarks: senile plaques (rich in amyloid-β peptide), neuronal fibrillary tangles (rich in phosphorylated tau protein), and synapse loss. However, definitive biomarkers for this devastating disease in living people are still lacking. In this study, we show that levels of oxidative stress markers are significantly increased in the mitochondria isolated from lymphocytes of subjects with mild cognitive impairment (MCI) compared to cognitively normal individuals. Further, an increase in mitochondrial oxidative stress in MCI is associated with MMSE score, vitamin E components, and β-carotene. Further, a proteomics approach showed that alterations in the levels of thioredoxin-dependent peroxide reductase, myosin light polypeptide 6, and ATP synthase subunit β might be important in the progression and pathogenesis of AD. Increased understanding of oxidative stress and protein alterations in easily obtainable peripheral tissues will be helpful in developing biomarkers to combat this devastating disorder. |
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| Keywords: | Proteomics Oxidative stress Alzheimer disease Mild cognitive impairment Lymphocytes Mitochondria Peripheral biomarker Free radicals |
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