Journal of Neural Transmission

, 116:1651 | Cite as

Elevated serum homocysteine level is not associated with serum C-reactive protein in patients with probable Alzheimer’s disease

  • Orhan Lepara
  • Azra Alajbegovic
  • Asija Zaciragic
  • Emina Nakas-Icindic
  • Amina Valjevac
  • Dzenana Lepara
  • Almira Hadzovic-Dzuvo
  • Almir Fajkic
  • Aida Kulo
  • Emin Sofic
Dementias - Original Article

Abstract

Elevated plasma homocysteine (Hcy) levels have been associated with Alzheimer’s disease (AD) and cognitive impairment. Studies have shown that Hcy may have direct and indirect neurotoxicity effects. The aim of the study was to investigate serum Hcy concentration in patients with probable AD with age-matched controls and to determine whether there was an association between serum Hcy and C-reactive protein concentration in patients with probable AD. We also aimed to determine whether there was an association between serum tHcy concentration and cognitive impairment in patients with probable AD. Serum concentration of total Hcy was determined by the fluorescence polarization immunoassay on the AxSYM system, and serum C-reactive protein (CRP) concentration was determined by means of particle-enhanced immunonephelometry with the use of BN II analyzer. Cognitive impairment was tested by the MMSE score. Body mass index (BMI) was calculated for each subject included in the study. Age, systolic and diastolic blood pressure and BMI did not differ significantly between the two groups. Mean serum tHcy concentration in the control group of subjects was 12.60 μmol/L, while in patients with probable AD the mean serum tHcy concentration was significantly higher than 16.15 μmol/L (p < 0.01). A significant negative association between serum tHcy concentration and cognitive impairment tested by the MMSE score in patients with probable AD was determined (r = −0.61634; p < 0.001). Positive, although not significant correlation between CRP and serum tHcy concentrations in patients with AD, was observed. Increased tHcy concentration in patients with probable AD, and the established negative correlation between serum tHcy concentration and cognitive damage tested by MMSE score in the same group of patients, suggests the possible independent role of Hcy in the pathogenesis of AD and cognitive impairment associated with this disease.

Keywords

Alzheimer’s disease Homocysteine C-reactive protein Cognitive impairment 

References

  1. Budge M, Johnston C, Hogervorst E, de Jager C, Milwain E, Iversen SD, Barnetson L, King E, Smith AD (2000) Plasma total homocysteine and cognitive performance in a volunteer elderly population. Ann N Y Acad Sci 903:407–410CrossRefPubMedGoogle Scholar
  2. Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM (1998) Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 55:1449–1455CrossRefPubMedGoogle Scholar
  3. Davis GK, Baboolal NS, Seales D, Ramchandani J, McKell S, McRae A (2007) Potential biomarkers for dementia in Trinidad and Tobago. Neurosci Lett 424:27–30CrossRefPubMedGoogle Scholar
  4. Gandy S (2005) The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease. J Clin Invest 115:1121–1129PubMedGoogle Scholar
  5. Gupta A, Watkins A, Thomas P, Majer R, Habubi N, Morris G, Pansari K (2005) Coagulation and inflammatory markers in Alzheimer’s and vascular dementia. Int J Clin Pract 59:52–57CrossRefPubMedGoogle Scholar
  6. Irizarry MC (2004) Biomarkers of Alzheimer disease in plasma. NeuroRx 1:226–234CrossRefPubMedGoogle Scholar
  7. Kalmijn S, Launer LJ, Lindemans J, Bots ML, Hofman A, Breteler MM (1999) Total homocysteine and cognitive decline in a community-based sample of elderly subjects: the Rotterdam Study. Am J Epidemiol 150:283–289PubMedGoogle Scholar
  8. Leblhuber F, Walli J, Artner-Dworzak E, Vrecko K, Widner B, Reibnegger G, Fuchs D (2000) Hyperhomocysteinemia in dementia. J Neural Transm 107:1469–1474CrossRefPubMedGoogle Scholar
  9. Lehman M, Gottfries CG, Regland B (1999) Identification of cognitive impairment in the elderly: homocysteine is an early marker. Dement Geriatr Cogn Disord 10:12–20CrossRefGoogle Scholar
  10. Licastro F, Pedrini S, Caputo L, Annoni G, Davis LJ, Ferri C, Casadei V, Grimaldi LM (2000) Increased plasma levels of interleukin-1, interleukin-6 and alpha-1-antichymotrypsin in patients with Alzheimer’s disease: peripheral inflammation or signals from the brain? J Neuroimmunol 103:97–102CrossRefPubMedGoogle Scholar
  11. Loncarević N, Mehmedika-Sulić E, Alajbegović A, Kucukalić A (2005) The neurologist role in diagnostics and therapy of the Alzheimer’s disease. Med Arh 59:106–109PubMedGoogle Scholar
  12. McCaddon A, Davies G, Hudson P, Tandy S, Cattell H (1998) Total serum homocysteine in senile dementia of Alzheimer type. Int J Geriatr Psychiatry 13:235–239CrossRefPubMedGoogle Scholar
  13. McGeer PL, McGeer EG (2002) Local neuroinflammation and the progression of Alzheimer’s disease. J Neurovirol 8:529–538CrossRefPubMedGoogle Scholar
  14. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944PubMedGoogle Scholar
  15. Nilsson K, Gustafson L, Hultberg B (2002) Relation between plasma homocysteine and Alzheimer’s disease. Dement Geriatr Cogn Disord 14:7–12CrossRefPubMedGoogle Scholar
  16. Pernet P, Lasnier E, Vaubourdolle M (2000) Evaluation of the AxSYM homocysteine assay and comparison with the IMx homocysteine assay. Clin Chem 46:1440–1441PubMedGoogle Scholar
  17. Poddar R, Sivasubramanian N, DiBello PM, Robinson K, Jacobsen DW (2001) Homocysteine induces expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human aortic endothelial cells: implications for vascular disease. Circulation 103:2717–2723PubMedGoogle Scholar
  18. Prins ND, Den Heijer T, Hofman A, Koudstaal PJ, Jolles J, Clarke R, Breteler MM (2002) Homocysteine and cognitive function in the elderly. The Rotterdam Scan Study. Neurology 59:1375–1380PubMedGoogle Scholar
  19. Quadri P, Fragiacomo C, Pezzati R, Zanda E, Forloni G, Tettamanti M, Lucca U (2004) Homocysteine, folate, and vitamin B12 in mild cognitive impairment, Alzheimer disease, and vascular dementia. Am J Clin Nutr 80:114–122PubMedGoogle Scholar
  20. Ravaglia G, Forti P, Maioli F, Muscari A, Sacchetti L, Arnone G, Nativio V, Talerico T, Mariani E (2003) Homocysteine and cognitive function in healthy elderly community dwellers in Italy. Am J Clin Nutr 77:668–673PubMedGoogle Scholar
  21. Ravaglia G, Forti P, Maioli F, Martelli M, Servadei L, Brunetti N, Porcellini E, Licastro F (2005) Homocysteine and folate as risk factors for dementia and Alzheimer disease. Am J Clin Nutr 82:636–643PubMedGoogle Scholar
  22. Riggs KM, Spiro A, Tucker K, Rush D (1996) Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study. Am J Clin Nutr 63:306–314PubMedGoogle Scholar
  23. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, Wilson PW, Wolf PA (2002) Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 346:476–483CrossRefPubMedGoogle Scholar
  24. Silbert B, Evered L, Scott DA, McCutcheon C, Jamrozik K (2008) Homocysteine and C-reactive protein are not markers of cognitive impairment in patients with major cardiovascular disease. Dement Geriatr Cogn Disord 25:309–316CrossRefPubMedGoogle Scholar
  25. Smith AD (2002) Homocysteine, B vitamins, and cognitive deficit in the elderly. Am J Clin Nutr 75:785–786PubMedGoogle Scholar
  26. Su SJ, Huang LW, Pai LS, Liu HW, Chang KL (2005) Homocysteine at pathophysiologic concentrations activates human monocyte and induces cytokine expression and inhibits macrophage migration inhibitory factor expression. Nutrition 21:994–1002CrossRefPubMedGoogle Scholar
  27. Yaffe K, Lindquist K, Penninx BW, Simonsick EM, Pahor M, Kritchevsky S, Launer L, Kuller L, Rubin S, Harris T (2003) Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology 61:76–80PubMedGoogle Scholar
  28. Zaciragic A, Lepara O, Valjevac A, Arslanagic S, Fajkic A, Hadzovic-Dzuvo A, Avdagic N, Alajbegovic A, Mehmedika-Suljic E, Coric G (2007) Elevated serum C-reactive protein concentration in Bosnian patients with probable Alzheimer’s disease. J Alzheimers Dis 12:151–156PubMedGoogle Scholar
  29. Zhang CE, Tian Q, Wei W, Peng JH, Liu GP, Zhou XW, Wang Q, Wang DW, Wang JZ (2008) Homocysteine induces tau phosphorylation by inactivating protein phosphatase 2A in rat hippocampus. Neurobiol Aging 29:1654–1665CrossRefPubMedGoogle Scholar
  30. Zhang CE, Wei W, Liu YH, Peng JH, Tian Q, Liu GP, Zhang Y, Wang JZ (2009) Hyperhomocysteinemia increases beta-amyloid by enhancing expression of gamma-secretase and phosphorylation of amyloid precursor protein in rat brain. Am J Pathol 174:1481–1491CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Orhan Lepara
    • 1
  • Azra Alajbegovic
    • 2
  • Asija Zaciragic
    • 1
  • Emina Nakas-Icindic
    • 1
  • Amina Valjevac
    • 1
  • Dzenana Lepara
    • 3
  • Almira Hadzovic-Dzuvo
    • 1
  • Almir Fajkic
    • 4
  • Aida Kulo
    • 5
  • Emin Sofic
    • 6
  1. 1.Institute of Physiology and Biochemistry, School of MedicineUniversity of SarajevoSarajevoBosnia and Herzegovina
  2. 2.Clinic for Neurology, Clinical CentreUniversity of SarajevoSarajevoBosnia and Herzegovina
  3. 3.Clinical Centre, Institute for Clinical Chemistry and BiochemistryUniversity of SarajevoSarajevoBosnia and Herzegovina
  4. 4.Institute of Pathophysiology, School of MedicalUniversity of SarajevoSarajevoBosnia and Herzegovina
  5. 5.Institute of Pharmacology, School of MedicineUniversity of SarajevoSarajevoBosnia and Herzegovina
  6. 6.Faculty of ScienceUniversity of SarajevoSarajevoBosnia and Herzegovina

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