5-10-methylenetetrahydrofolic-acid and Alzheimer-Disease

Decreased serum concentrations of vitamin B12 are associated with Alzheimer's type dementia. The transcobalamin II gene (TCN2) 776C → G polymorphism affects transcobalamin II function as a carrier of vitamin B12 and might modify its availability. The association of the TCN2 776C → G polymorphism with Alzheimer's type dementia is unclear and was investigated in the present study.. Case-control study including 27 individuals diagnosed with Alzheimer's type dementia and 28 healthy controls. Serum concentrations of vitamin B12, homocysteine and other analytes were determined and the presence of TCN2 776C → G and 5, 10-methylenetetrahydrofolate reductase 1298A → C polymorphisms genotypes was ascertained by polymerase chain reaction-restriction fragment length polymorphism.. Serum concentrations of vitamin B12 were lower while those of homocysteine were higher in patients than in controls (P < 0.05). The frequency of individuals carrying at least one 5, 10-methylenetetrahydrofolate reductase 1298C allele was higher (59% versus 32%) while frequency of individuals harbouring at least one TCN2 776G allele was lower (58% versus 86%) in patients than in controls (P < 0.05). Univariate logistic regression showed negative association of TCN2 776CG genotype with Alzheimer's type dementia (OR = 0.17 versus CC genotype, P < 0.02). Multivariate logistic regression identified TCN2 776C → G polymorphism as independent predictor of Alzheimer's type dementia together with higher concentrations of homocysteine, cholesterol and uric acid and lower concentrations of oestradiol. Association of TCN2 776C → G polymorphism with Alzheimer's type dementia was observed for individuals carrying the 5,10-methylenetetrahydrofolate reductase 1298AA genotype but not the AC or CC genotypes, indicating interaction between the two polymorphisms.. The TCN2 776C → G polymorphism is negatively associated with Alzheimer's type dementia, suggesting a protective role against the disease in subjects with the 5, 10-methylenetetrahydrofolate reductase 1298AA genotype.

Topics: Aged; Alleles; Alzheimer Disease; Biomarkers; Case-Control Studies; Female; Gene Frequency; Genotype; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Prognosis; Tetrahydrofolates; Transcobalamins; Vitamin B 12

To study the interplay between serum concentrations of homocysteine, steroid hormones and vitamins B and mutations in 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, in association to Alzheimer's type dementia (ATD).. Case-control study including 19 individuals diagnosed with ATD and 36 healthy controls. Serum concentrations of the analytes were determined and MTHFR 1298A-->C mutation was screened by PCR-RFLP.. Multivariable logistic regression analysis identified homocysteine (OR=1.92, P<0.01), cholesterol (OR=1.14, P<0.001), estradiol (OR=0.728, P<0.001), uric acid (OR=2.42, P<0.02), vitamin B(12) (OR=0.984, P<0.004) and MTHFR 1298A-->C mutation (OR=6.01, P<0.04) as independent predictors of ATD. Positive interaction between homocysteine and uric acid, creatinine, urea or cortisol (P<0.02) and negative interaction between homocysteine and vitamin B(12) or MTHFR 1298A-->C mutation (P<0.03) were observed.. High serum concentrations of homocysteine, cholesterol and uric acid, and low concentrations of estradiol and vitamin B(12), as well as the MTHFR 1298A-->C mutation are simultaneously associated to ATD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; C-Reactive Protein; Case-Control Studies; Estradiol; Female; Homocysteine; Humans; Male; Middle Aged; Mutation; Polymorphism, Restriction Fragment Length; Testosterone; Tetrahydrofolates; Urea; Uric Acid

Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are accompanied by increased levels of 8-oxo-2'-deoxyguanosine (8-oxo2dG) and alterations in levels of homocysteine (Hcy), methionine (Met), and cysteine (Cys). Hcy may undergo remethylation due to involvement of MTHFR, MTR and MTHFD1 proteins. Present studies are aimed at determination of 8-oxo2dG, Hcy, Met, and Cys in AD and PD patients as well as in control groups, using HPLC/EC/UV, as well as estimation, by restriction analysis, frequency of following gene polymorphisms: MTHFR (C677T, A1298C, G1793A), MTHFD1 (G1958A), and MTR (A2756G). In AD there were significant differences of the levels of only Cys (GG, MTHFR, G1793A) and Met/Hcy (AA, MTHFD1, G1958A) whereas in PD there were more significant differences of the levels of thiols: Hcy [MTHFR: CT (C677T) and GG (G1793A); MTR, AG (A2756G)], Met [MTR, AA (A2756G)], Cys [MTR, AG (A2756G)], and Met/Hcy [MTHFR: CC, CT (C677T) and AA (A1298C), and GG (G1793A); MTHFD1 AA(G1958A); MTR AA(A2756G)]. Significant differences in the levels of Cys/Hcy, MTHFD1 GA (G1958) were varied between AD and PD groups. The results indicate that of the enzymes studied only polymorphisms of folate-dependent enzyme MTHFD1 have pointed to significant differences in intensity of turnover of circulating thiols between AD and PD patients.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Alzheimer Disease; Analysis of Variance; Cysteine; Deoxyguanosine; DNA Damage; DNA Mutational Analysis; Female; Homocystine; Humans; Male; Methionine; Methylenetetrahydrofolate Dehydrogenase (NADP); Middle Aged; Parkinson Disease; Polymorphism, Genetic; Sulfhydryl Compounds; Tetrahydrofolates

The epsilon4 allele of apolipoprotein E (APOE), and the plasma levels of APOE, amyloid beta-protein precursor, amyloid beta1-40 (Abeta40) and homocysteine (Hcy) have all been correlated with the presence of dementia. Mutations in the methylnetetrahydrofolate reductase enzyme (MTHFR) have been associated with elevated levels of Hcy. This study explored the association of these factors with cognition and depression in community dwelling older men. Two hundred and ninety-nine men, mean age 78.9 years (SD 2.8), were studied in this cross-sectional survey. Mean plasma Hcy was 13.5 (SD 5.3) micromol/L. The MTHFR genotype had no obvious impact on Hcy levels. Ln Hcy and Ln Abeta40 were both inversely correlated with calculated glomerular filtration rate (cGFR), r = -0.41 (p < 0.001) and r = -0.28 (p < 0.001), respectively. There was a positive correlation between Ln Hcy and Ln Abeta40, r = 0.19 (p < 0.001), which remained significant after adjusting for cGFR, with a doubling of Hcy associated with a 24% increase of Abeta40. The e4 allele was associated with increased depressive symptoms as measured by the Geriatric Depression Scale-15, Odds ratio (OR) = 2.59 (95%CI 1.06-6.34) and poorer performance on the Clock Drawing Test, OR = 2.32 (95% CI: 1.25-4.29). There was a positive association between Abeta40 and Hcy, even after adjustment for cGFR in this sample of well, community dwelling older men. This association may help elucidate the link between elevated levels of Hcy and Alzheimer's disease.

Topics: Aged; Alzheimer Disease; Amyloid beta-Protein Precursor; Apolipoproteins E; Cognition Disorders; Cross-Sectional Studies; Depression; Gene Expression; Homocysteine; Humans; Male; Neuropsychological Tests; Point Mutation; Polymerase Chain Reaction; Severity of Illness Index; Surveys and Questionnaires; Tetrahydrofolates