Lymphocyte mitochondria: toward identification of peripheral biomarkers in the progression of Alzheimer disease.
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.
Department of Chemistry, Center of Membrane Sciences, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA.
Rukhsana
R
Sultana
Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
Mauro
M
Baglioni
Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
Roberta
R
Cecchetti
Department of Nephrology and Proteomics Center, University of Louisville, Louisville, KY 40292, USA.
Jian
J
Cai
Department of Nephrology and Proteomics Center, University of Louisville, Louisville, KY 40292, USA.
Jon B
JB
Klein
Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
Patrizia
P
Bastiani
Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
Carmelinda
C
Ruggiero
Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. Electronic address: mecocci@unipg.it.
Patrizia
P
Mecocci
Department of Chemistry, Center of Membrane Sciences, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA. Electronic address: dabcns@uky.edu.
D Allan
DA
Butterfield
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis*; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000378:metabolism; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007525:Isoelectric Focusing; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D040901:Proteomics
D015415:Biomarkers
Alzheimer disease; Free radicals; Lymphocytes; Mild cognitive impairment; Mitochondria; Oxidative stress; Peripheral biomarker; Proteomics