Homocysteine, Apolipoproteine E and Methylenetetrahydrofolate Reductase in Alzheimer’s Disease and Mild Cognitive Impairment

Abstract

Background: Alzheimer’s disease (AD) is the most common dementia disorder in elderly people. Currently, the only known genetic factor associated with the development of sporadic AD is the apolipoprotein E (ApoE) 4 allele. There is a need to identify other environmental and genetic risk factors that could modulate the risk of developing sporadic AD. Objective: To analyse the correlation between the ApoE and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and plasma homocysteine levels and vitamins (B₁₂ and folic acid) concentrations in serum from patients with AD and mild cognitive impairment (MCI) as compared with control group. Methods: The study was carried out in 99 AD patients, 98 subjects with MCI and 100 healthy subjects. Diagnosis of probable AD was made according to the NINCDS-ADRDA and DSM-IV criteria. The following factors were analysed: age, gender, duration of disease, concentration of plasma total homocysteine, folic acid and vitamin B₁₂ in the serum and the polymorphism of MTHRF and ApoE genes. The results obtained were analysed by multivariate analysis of regression. Results: We found that plasma total homocysteine is increased in AD patients (p < 0.0001) and depended on the MTHFR T/T genotype in the presence of low folate levels (p < 0.05). The increased frequency of ApoE4 allele in the AD population was independent of homocysteine, folic acid and vitamin B₁₂ levels and MTHFR status. Conclusions: We conclude that the concentration of plasma total homocysteine is increased in AD patients. This may be associated with the T/T genotype in the MTHFR gene; however, the distribution of the MTHRF C677T polymorphism in the Polish population does not differ in AD and controls.

Homocysteine and asymmetric dimethylarginine concentrations in the plasma of Alzheimer’s disease patients with varying degrees of dementia

“…Previous studies show that there are no differences in plasma Hcy levels or the progression of cognitive impairment between APOE4 carriers and noncarriers in the Polish population and refer to the papers by Religa et al [11] and Siuda et al [12].…”

The Mthfr 677t Allele May Influence the Severity and Biochemical Risk Factors of Alzheimer'Sdisease in an Egyptian Population

“…As shown in Table 4, the frequencies of the T allele and of the homozygous mutant genotype 677T/T in our Egyptian population (38.4% and 18.6%, resp.) are midway between the frequencies in Caucasians, who have the lowest frequencies [20], and East Asians, who have the highest frequencies [30].…”

“…There are cross-population differences in the frequency of the 677T/T genotype in patients with AD, ranging from 8% in Caucasian-Polish populations to 44% in East Asian (Chinese) [30]. In addition, the 677T allele frequency ranges from 27-30% in Polish populations [20] to 62% in Korean populations [32].…”

Folate Pathway Gene Methylenetetrahydrofolate Reductase C677T Polymorphism and Alzheimer Disease Risk in Asian Population

“…Several epidemiological and experimental studies have linked folate deficiency and resultant increased Hcy levels with AD. Polymorphism of folate metabolizing gene MTHFR C677T may predispose individuals to elevated plasma levels of Hcy [35,36]. MTHFR is an essential enzyme in the folate mediated one-carbon transfer reactions and any genetic deficiency in this enzyme could induce severe hyperhomocysteinemia [37].…”