Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer's Disease

Seshadri, Sudha; Beiser, Alexa; Selhub, Jacob; Jacques, Paul F.; Rosenberg, Irwin H.; D’Agostino, Ralph B.; Wilson, Peter W.F.; Wolf, Philip A.

doi:10.1056/nejmoa011613

Cited by 2,953 publications

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“…1 Hyperhomocysteinemia has also been linked to increased risk of Alzheimer's disease, 2 neural tube defects, 3 complications during pregnancy, 4 inflammatory bowel disease, 5 and osteoporosis. 6 The role of Hcy in disease is unclear.…”

Section: Homocysteine and Cysteine In Human Healthmentioning

confidence: 99%

“…Two of the many characteristic reactions of thiyl radicals include the formation of a reducing disulfide radical anion (eq 1) (1) and the formation of a reducing α-amino carbon-centered radical (eq 2). (2) The analogous process in eq 2, which proceeds intermolecularly, is involved in "repairing" processes targeting the carbon-centered radicals of biomolecules. 30 The formation of the α-amino alkyl radical of Cys was reported in 1971 by Neta.…”

Section: The Redox Chemistry Of Biological Thiols and Selective Hcy Dmentioning

confidence: 99%

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Detection of Homocysteine and Cysteine

et al. 2005

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At elevated levels, homocysteine (Hcy, 1) is a risk factor for cardiovascular diseases, Alzheimer's disease, neural tube defects, and osteoporosis. Both 1 and cysteine (Cys, 3) are linked to neurotoxicity. The biochemical mechanisms by which 1 and 3 are involved in disease states are relatively unclear. Herein, we describe simple methods for detecting either Hcy or Cys in the visible spectral region with the highest selectivity reported to date without using biochemical techniques or preparative separations. Simple methods and readily available reagents allow for the detection of Cys and Hcy in the range of their physiologically relevant levels. New HPLC postcolumn detection methods for biological thiols are reported. The potential biomedical relevance of the chemical mechanisms involved in the detection of 1 is described.

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Section: Homocysteine and Cysteine In Human Healthmentioning

confidence: 99%

Section: The Redox Chemistry Of Biological Thiols and Selective Hcy Dmentioning

confidence: 99%

Detection of Homocysteine and Cysteine

et al. 2005

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“…Elevated tHcy represents a major risk factor of cardiovascular and cerebrovascular diseases (Homocysteine Studies Collaboration 2002). Moreover, lower serum folate and higher plasma tHcy may also be causes of neural tube defects (NTDs) (Smithells et al 1976; Daly et al 1995), cognitive dysfunction (Seshadri et al 2002), and depression (Bottiglieri 2005). …”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms and folate status

Hiraoka

Kagawa

2017

Congenital Anomalies

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Moderate hyperhomocysteinemia‐induced low folate status is an independent risk factor for cardiovascular disease, dementia, and depression. Folate is an essential cofactor in the one‐carbon metabolism pathway and is necessary in amino acid metabolism, purine and thymidylate synthesis, and DNA methylation. In the folate cycle and homocysteine metabolism, folate, vitamin B12, vitamin B6, and vitamin B2 are important cofactors. Many enzymes are involved in folate transport and uptake, the folate pathway, and homocysteine (Hcy) metabolism, and various polymorphisms have been documented in these enzymes. Serum folate and total Hcy (tHcy) levels are influenced by folate intake and genetic polymorphisms in 5,10‐methylenetertahydrofolate reductase (MTHFR) such as C677T. The prevalence of the MTHFR 677TT genotype varies across ethnic groups and regions, with a frequency of approximately 15% in Japanese populations. Individuals with the TT genotype have significantly higher tHcy levels and lower folate levels in serum than those with the CT and TT genotypes. However, administration of folic acid has been shown to eliminate these differences. Moreover, data have suggested that interventions based on genotype may be effective for motivating individuals to change their lifestyle and improve their nutrition status. Accordingly, in this review, we discuss the effects of MTHFR C677T polymorphisms on serum tHcy and folate levels with folic acid intervention and evaluate approaches for overcoming folic acid deficiency and related symptoms.

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“…However, even in the absence of anaemia, suboptimal vitamin B 12 status may exist and this places older people at increased risk of neurological abnormalities (Lindenbaum et al, 1988). Further, low serum vitamin B 12 concentrations lead to elevated homocysteine concentrations, which are associated with an increased risk of ischaemic heart disease (Ford et al, 2002) and Alzheimer's Disease (Seshadri et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Serum vitamin B12 concentrations and atrophic gastritis in older New Zealanders

et al. 2004

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Objective: To determine the serum vitamin B 12 status of older New Zealanders and to assess the impact of atrophic gastritis on vitamin B 12 status. Design: A cross-sectional nationally representative population-based survey. Method: Serum vitamin B 12 concentrations were used to assess vitamin B 12 status. The presence and severity of atrophic gastritis was classified using serum pepsinogen I and II. Subjects: A total of 466 noninstitutionalized urban and rural dwelling New Zealanders aged 65 y or older who participated in the 1997 National Nutrition Survey. Results: The prevalence of deficient (o148 pmol/l) and marginal (148-221 pmol/l) serum vitamin B 12 concentrations was 12 and 28%, respectively. The prevalence of atrophic gastritis was 6.7% (severe 3.1%, mild-moderate 3.6%). While atrophic gastritis increased the relative risk (RR, 95% CI) of having a deficient or marginal serum vitamin B 12 concentration by 21-fold (6-67) and five-fold (1-17), respectively, those who had atrophic gastritis made up only 33 and 6% of the participants with deficient or marginal serum vitamin B 12 concentrations. An intake of vitamin B 12 from food that exceeded the recommended dietary allowance (2.4 mg/day) did not protect against deficient (RR 0.5; 95% CI: 0.2, 1.2) or marginal (RR 0.9; 95% CI: 0.5, 1.7) serum vitamin B 12 status. Vitamin B 12 supplement users had a reduced risk of having deficient and marginal vitamin B 12 status (RR 0.3; 95% CI: 0.1, 0.8).Conclusions: There is a relatively high prevalence of deficient and marginal serum vitamin B 12 concentrations among older New Zealanders. However, the prevalence of atrophic gastritis was low in the New Zealand elderly compared with other surveys. Although atrophic gastritis was a risk factor for low vitamin B 12 status, it did not fully explain the prevalence of low serum vitamin B 12 .

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Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer's Disease

Abstract: An increased plasma homocysteine level is a strong, independent risk factor for the development of dementia and Alzheimer's disease.

Cited by 2,953 publications

References 51 publications

Detection of Homocysteine and Cysteine

Detection of Homocysteine and Cysteine

Genetic polymorphisms and folate status

Serum vitamin B12 concentrations and atrophic gastritis in older New Zealanders

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