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Role of Homocysteine in Cognitive Impairement and Alzheimer’s Disease

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Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

A high circulating concentration of the non proteinogenic amino acid homocysteine has been implicated as a risk factor for Alzheimer’s Disease and its prodromal stage, mild cognitive impairement. Furthermore, hyperhomocysteinaemia has been directly attributed to a deficiency in vitamins B12, folate, and B6. Several studies have demonstrated decrease in progression of mild cognitive impairement to Alzheimer’s Disease, and some have even shown an improvement in cognition after vitamin supplements with B12 and folate. Plausible mechanisms linking hyperhomocysteinaemia to Alzheimer’s and cognitive impairement have been hypothesized and demonstrated in hyperhomocysteinemic mice models. However, some studies have not elucidated any benefit of vitamin supplements in subjects with cognitive impairment. Hence, multicentric clinical studies need to be conducted to substantiate the mechanisms of neuronal degeneration due to hyperhomocysteinaemia and to demonstrate the beneficial effect of folate, B6 and B12 supplements on cognition.

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References

  1. Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013;9(2):106–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bhargava S, Srivastava LM. Homocysteine—Marker of the millenium—a review of its evolution and clinical implication. J Med Sci. 2001;4(2):104–16.

    Google Scholar 

  3. Bhargava S, Parakh R, Manocha A, Kankra M, Aggarwal CS, Menon G, et al. High prevalence of hyperhomocysteinemia among Indian patients of vascular disease. Clin Chim Acta. 2006;374(1–2):160–2.

    Article  CAS  PubMed  Google Scholar 

  4. Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer Disease—The Nun Study. JAMA. 1997;277(10):813–7.

    Article  CAS  PubMed  Google Scholar 

  5. Neuropathology Group. Medical Research Council Cognitive Function and Aging Study. Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Lancet. 2001;357(9251):169–75.

    Article  Google Scholar 

  6. McCaddon A, Davies G, Hudson P, Tandy S, Cattell H. Total serum homocysteine in senile dementia of Alzheimer type. Int J Geriatr Psychiatry. 1998;13:235–9.

    Article  CAS  PubMed  Google Scholar 

  7. Wang HX, Wahlin A, Basun H, Fastbom J, Winblad B, Fratiglioni L. Vitamin B12 and folate in relation to the development of Alzheimer’s disease. Neurology. 2001;56:1188–94.

    Article  CAS  PubMed  Google Scholar 

  8. Williams JH, Pereira EA, Budge MM, Bradley KM. Minimal hippocampal width relates to plasma homocysteine in community-dwelling older people. Age Ageing. 2002;31:440–4.

    Article  PubMed  Google Scholar 

  9. Kruman II, Kumaravel TS, Lohani A, Pedersen WA, Cutler RG, Kruman Y, et al. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer’s disease. J Neurosci. 2002;22:1752–62.

    CAS  PubMed  Google Scholar 

  10. Mallroy SP, Dynan KB, Lawson JT, Patterson CC, Passmore AP. Moderately elevated plasma homocysteine, methylenetetrahydrofolate reductase genotype, and risk for stroke, vascular dementia, and Alzheimer disease in Northern Ireland. Stroke. 2002;33:2351–6.

    Article  Google Scholar 

  11. Qadri P, Fragiacomo C, Pezzati R, Zanda E, Forloni G, Tettamanti M, et al. Homocysteine, folate and vitamin B-12 in mild cognitive impairment, Alzheimer’s Disease and vascular dementia. Am J Clin Nutr. 2004;80:114–22.

    Google Scholar 

  12. Schafer JH, Glass TA, Bolla KI, Mintz M, Jedlicka AE, Shwartz BS. Homocysteine and cognitive function in a population-based study of older adults. J Am Geriatr Soc. 2005;53:381–8.

    Article  PubMed  Google Scholar 

  13. Bhargava S, Ali A, Bhargava EK, Manocha A, Kankra M, Das S, et al. Lowering homocysteine and modifying nutritional status with folic acid and vitamin B12 in Indian patients of vascular disease. J Clin Biochem Nutr. 2012;50(3):222–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. McCaddon A. Homocysteine and cognitive impairment—a case series in a general practice setting. Nutr J. 2006;5:6.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Aisen PS, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, Weiner MF, et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. 2008;300:1774–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Malouf M, Grimley EJ, Areosa SA. Folic acid with or without B12 for cognition and dementia. Cochrane Database Syst Rev 2003; (4):CD004514.

  17. Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS ONE. 2010;5(9):e12244.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Smach MA, Jacob N, Golmard JL, Charfeddine B, Lammouchi T, Ben Othman L, et al. Folate and homocysteine in the cerebrospinal fluid of patients with Alzheimer’s disease or dementia: a case control study. Eur Neurol. 2011;65(5):270–8.

    Article  CAS  PubMed  Google Scholar 

  19. Zheng L, Kong X, Cui Y, Wei Y, Zhang J, Wei W. Conversion from MCI to AD in patients with the APOE ε4 genotype: prediction by plasma HCY and serum BDNF. Neurosci Lett. 2016;626:19–24.

    Article  CAS  PubMed  Google Scholar 

  20. Lee HK, Kim SY, Sok SR. Effects of Multivitamin Supplements on Cognitive Function, Serum Homocysteine Level, and Depression of Korean Older Adults With Mild Cognitive Impairment in Care Facilities. J Nurs Scholarsh. 2016;48(3):223–31.

    Article  PubMed  Google Scholar 

  21. Lomnadze D, Roberts AM, Tyagi N, Moshal KS, Tyagi SC. Homocysteine causes cerebrovascular leakage in mice. Am J Physiol Heart Circ Physiol. 2006;290(3):H1206.

    Article  Google Scholar 

  22. Kumar M, Tyagi N, Moshal KS, Sen U, Kundu S, Mishra PK, et al. Homocysteine reduces blood flow to brain due to vascular resistance in carotid artery. Neurochem Int. 2008;53(6–8):214–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bhargava S, Pushpakumar S, Metreveli N, Givvimani S, Tyagi SC. MMP-9 gene ablation mitigates hyperhomocysteinemia-induced cognition and hearing dysfunction. Mol Biol Rep. 2014;41(8):4889–98.

    Article  CAS  PubMed  Google Scholar 

  24. Chan AY, Alsaraby A, Shea TB. Folate deprivation increases tau phosphorylation by homocysteine-induced calcium influx and by inhibition of phosphatase activity: alleviation by S-adenosyl methionine. Brain Res. 2008;1199:133–7.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry and Professor, GRIPMER, Sir Ganga Ram Hospital, New Delhi, India

    Seema Bhargava

  2. Department of Biochemistry, Sir Ganga Ram Hospital, New Delhi, India

    Annsh Bhandari

  3. Department of Research, Sir Ganga Ram Hospital, New Delhi, India

    Sangeeta Choudhury

Authors
  1. Seema Bhargava
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  2. Annsh Bhandari
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  3. Sangeeta Choudhury
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Correspondence to Seema Bhargava.

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Bhargava, S., Bhandari, A. & Choudhury, S. Role of Homocysteine in Cognitive Impairement and Alzheimer’s Disease. Ind J Clin Biochem 33, 16–20 (2018). https://doi.org/10.1007/s12291-017-0646-5

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  • DOI: https://doi.org/10.1007/s12291-017-0646-5

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