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Evaluation of Selenium, Redox Status and Their Association with Plasma Amyloid/Tau in Alzheimer’s Disease

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Abstract

The aim of the study was to evaluate blood selenium and antioxidants as possible oxidative stress markers in Alzheimer’s disease (AD) along with amyloid β42 (Aβ42) and tau by comparing them with vascular dementia (VD) and age-matched healthy controls. Selenium, total tau, Aβ42, glutathione (GSH) and malondialdehyde (MDA) levels and the activities of antioxidant enzymes were analysed in the blood of AD patients (n = 30), VD patients (n = 35) and controls (n = 40) from South India. Plasma Aβ42 level was significantly higher (P < 0.001) in both AD and VD compared to controls. Total tau and tau-to-amyloid ratio were significantly lower in both AD and VD (P < 0.001), compared to controls, and a significant difference (P < 0.01 and P < 0.05, respectively) was also observed between AD and VD. The receiver operating characteristic (ROC) curve-derived cutoff values of <3.5 for tau-to-Aβ42 ratio and <520 pg/ml for total tau showed sensitivity and specificity of around 67–72 % for differentiating AD from VD and around 90 % for AD from controls, indicating that they could serve as reliable AD-specific markers. The MDA levels were significantly higher (P < 0.001) in both dementia groups along with a significant decrease (P < 0.001) in reduced GSH levels, indicating elevated oxidative stress and altered redox status in both forms of dementia. Selenium levels did not vary significantly between the three groups. The activity of glutathione peroxidase increased in both AD and VD compared to controls, with a concomitant decrease in glutathione reductase and glucose-6-phospate dehydrogenase (P < 0.001) activity. The activity of thioredoxin reductase was significantly lower in both patient groups (P < 0.001) compared to healthy controls. No correlation was observed between selenium and activities of selenoenzymes, tau, Aβ42 or tau-to-Aβ42 ratio, when analysing independently, indicating that blood selenium may not be directly involved in Aβ production and in regulating tau/Aβ42-mediated mechanism in AD. The present study emphasizes the enhanced oxidative stress in AD pathology and plasma tau and tau-to-amyloid ratio as possible markers to differentiate AD from VD. The study also points that blood selenium may not be involved in regulating oxidative stress in AD, and a longitudinal study correlating plasma and cerebrospinal fluid (CSF) selenium and selenoprotein levels is warranted.

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References

  1. Shaji KS, Jotheeswaran AT, Girish N, et al (2010) Dementia India Report: prevalence, impact, costs and services for dementia. Alzheimer’s & Related Disorders Society of India. http://www.alzheimer.org.in/assets/dementia.pdf. Accessed 25 Aug 2013

  2. Zawia NH, Lahiri DK, Cardozo-Pelaez F (2009) Epigenetics, oxidative stress and Alzheimer’s disease. Free Readic Biol Med 46:1241–1249

    Article  CAS  Google Scholar 

  3. Padurariu M, Ciobica A, Hritcu L et al (2010) Changes of some oxidative stress markers in the serum of patients with mild cognitive impairment and Alzheimer’s disease. Neurosci Lett 469:6–10

    Article  PubMed  CAS  Google Scholar 

  4. Butterfield DA, Swomley AM, Sultana R (2013) Amyloid β-peptide (1-42)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression. Antioxid Redox Signal 19:823–835

    Article  PubMed  CAS  Google Scholar 

  5. Puertas MC, Martinez-Martos JM, Cobo MP et al (2012) Plasma oxidative stress parameters in men and women with early stage Alzheimer type dementia. Exp Gerontol 47:625–630

    Article  PubMed  CAS  Google Scholar 

  6. Casado A, Lopez-Fernandez ME, Casado MC et al (2008) Lipid peroxidation and antioxidant enzyme activities in vascular dementia and Alzheimer dementias. Neurochem Res 33:450–458

    Article  PubMed  CAS  Google Scholar 

  7. Naziroğlu M (2007) New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res 32:1990–2001

    Article  PubMed  CAS  Google Scholar 

  8. Naziroğlu M (2012) Molecular role of catalase on oxidative stress-induced Ca2+ signalling and TRP channel activation in nervous system. J Recept Signal Transduct Res 32:134–141

    Article  PubMed  CAS  Google Scholar 

  9. Naziroğlu M, Yürekli VA (2013) Effects of antiepileptic drugs on antioxidant and oxidant molecular pathways: focus on trace elements. Cell Mol Neurobiol 33:589–599

    Article  PubMed  CAS  Google Scholar 

  10. Gwon AR, Park JS, Park JH et al (2010) Selenium attenuates A beta production and A beta-induced neuronal death. Neurosci Lett 469:391–395

    Article  PubMed  CAS  Google Scholar 

  11. Steinbrenner H, Sies H (2013) Selenium homeostasis and antioxidant selenoproteins in brain: implications for disorders in the central nervous system. Arch Biochem Biophys 536:152–157

    Article  PubMed  CAS  Google Scholar 

  12. Akbaraly NT, Hininger-Favier I, Carriere I et al (2007) Plasma selenium over time and cognitive decline in the elderly. Epidemiology 18:52–58

    Article  PubMed  Google Scholar 

  13. Loef M, Schrauzer GN, Walach H (2011) Selenium and Alzheimer’s disease: a systematic review. J Alzheimers Dis 26:81–104

    PubMed  CAS  Google Scholar 

  14. Kapaki E, Paraskevas GP, Zalonis I et al (2003) CSF tau protein and beta-amyloid (1-42) in Alzheimer's disease diagnosis: discrimination from normal ageing and other dementias in the Greek population. Eur J Neurol 10:119–128

    Article  PubMed  CAS  Google Scholar 

  15. Mayeux R, Honig LS, Tang MX et al (2003) Plasma Aβ40 and Aβ42 and Alzheimer’s disease. Relation to age, mortality and risk. Neurology 61:1185–1190

    Article  PubMed  CAS  Google Scholar 

  16. Sparks DL, Kryscio RJ, Sabbagh MN et al (2012) Tau is reduced in AD plasma and validation of employed ELISA methods. Am J Neurodegener Dis 1:99–106

    PubMed Central  PubMed  Google Scholar 

  17. Sunderland T, Linker G, Mirza N et al (2003) Decreased β amyloid 1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer’s disease. JAMA 289:2094–2103

    Article  PubMed  Google Scholar 

  18. Rice-Evans C (1996) Free radicals and antioxidants in atherosclerosis. In: Blake D, Winyard PG (eds) Immunopharmacology of free radical species. Academic, London, pp 39–52

    Google Scholar 

  19. Folstein MF, Folstein SE, Mc Hugh PR (1975) “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    Article  PubMed  CAS  Google Scholar 

  20. Rani P, Unni M, Karthikeyan J (2004) Evaluation of antioxidant properties of berries. Indian J Clin Biochem 19:103–110

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  22. Drabkin DL, Austin JH (1935) Spectrophotometric studies II. Preparations from washed blood cells; nitric oxide haemoglobin and sulfhaemoglobin. J Biol Chem 112:51–65

    CAS  Google Scholar 

  23. Safaralizadeh R, Kardar GA, Pourpak Z et al (2005) Serum concentrations of selenium in healthy individuals living in Tehran. Nutr J 4:32–35

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  24. Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    PubMed  CAS  Google Scholar 

  25. Arner ES, Zhong L, Holmgren A (1999) A preparation and assay of mammalian thioredoxin and thioredoxin reductase. Methods Enzymol 300:226–239

    Article  PubMed  CAS  Google Scholar 

  26. Das K, Samanta L, Chainy GBN (2000) A modified spectrophotometric assay of superoxide dismutase using nitrite formation by superoxide radicals. Indian J Biochem Bio 37:201–204

    CAS  Google Scholar 

  27. Calberg I, Mannervik J (1985) Glutathione reductase. Methods Enzymol 113:484–490

    Article  Google Scholar 

  28. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  PubMed  CAS  Google Scholar 

  29. Lobarzewski J, Ginalska G (1995) Industrial use of soluble or immobilized plant peroxidases. Plant peroxidase Newsletter 6:3–7

    Google Scholar 

  30. Balinsky D, Bernstein RR (1963) The purification and properties of glucose-6-phosphate dehydrogenase from human erythrocytes. Biochim Biophy Acta 67:313–315

    Article  CAS  Google Scholar 

  31. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophy 82:70–77

    Article  CAS  Google Scholar 

  32. Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    Article  PubMed  CAS  Google Scholar 

  33. Roher AE, Esh CL, Kokjohn TA et al (2009) Aβ peptides in human plasma and their significance for Alzheimer’s disease. Alzheimers Dement 5:18–29

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  34. Toledo JB, Shaw LM, Trojanowski JQ (2013) Plasma amyloid beta measurements—a desired but elusive Alzheimer’s disease biomarker. Alzheimers Res Ther 5:8–17

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  35. Klapinska B, Poprezecki S, Danch A et al (2005) Blood selenium concentration of residents of upper Silesia: relation to age and gender. Polish J of Environ Stud 15:753–758

    Google Scholar 

  36. van Eersel J, Ke YD, Liu X et al (2010) Sodium selenate mitigates tau pathology, neurodegeneration and functional deficits in Alzheimer’s disease. Proc Natl Acad Sci U S A 107:13888–13893

    Article  PubMed Central  PubMed  Google Scholar 

  37. Bellinger FP, He Q, Bellinger MT et al (2008) Association of selenoprotein P with Alzheimer’s pathology in human cortex. J Alzheimers Dis 15:465–472

    PubMed Central  PubMed  CAS  Google Scholar 

  38. Strozyk D, Launer LJ, Adlard PA et al (2009) Zinc and copper modulate Alzheimer Abeta levels in human cerebrospinal fluid. Neurobiol Aging 30:1069–1077

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  39. Naziroğlu M (2009) Role of selenium on calcium signalling and oxidative stress induced molecular pathways in epilepsy. Neurochem Res 34:2181–2191

    Article  PubMed  CAS  Google Scholar 

  40. Gil L, Siems W, Mazurek B et al (2006) Age-associated analysis of oxidative stress parameters in human plasma and erythrocytes. Free Radial Res 40:495–505

    Article  CAS  Google Scholar 

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Acknowledgments

The study was supported by the Indian Council of Medical Research (ICMR) and Department of Biotechnology (DBT), New Delhi. The authors thank Dr. M.B. Pranesh, PSG IMS&R, Coimbatore, and Dr. Jacob Roy, ARDSI, Thrissur, for referring patients for the study.

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  1. Department of Biotechnology, PSG College of Technology, Peelamedu, Coimbatore, Tamil Nadu, 641004, India

    Sreeram Krishnan & P. Rani

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  1. Sreeram Krishnan
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  2. P. Rani
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Correspondence to P. Rani.

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Krishnan, S., Rani, P. Evaluation of Selenium, Redox Status and Their Association with Plasma Amyloid/Tau in Alzheimer’s Disease. Biol Trace Elem Res 158, 158–165 (2014). https://doi.org/10.1007/s12011-014-9930-x

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  • DOI: https://doi.org/10.1007/s12011-014-9930-x

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