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Plasma folate, vitamin B(12), and total homocysteine and homozygosity for the C677T mutation of the 5,10-methylene tetrahydrofolate reductase gene in patients with Alzheimer's dementia. A case-control study.

Abstract

BACKGROUND

Elevated total plasma homocysteine (tHcy) levels are considered a risk factor for cerebrovascular disease and may also play an important role in the pathogenesis of Alzheimer's disease (AD). High values of plasma tHcy and low levels of vitamin B(12) and folate are frequently present in AD patients. Moreover, the homozygous mutation (C677T) of the methylene tetrahydrofolate reductase (MTHFR) gene, related to a thermolabile type of the encoded enzyme, causes hyperhomocysteinemia by reducing the 5-methyltetrahydrofolate availability.

OBJECTIVE

The aim of the study was to investigate plasma levels of folate, vitamin B(12) and tHcy in patients with AD. These values were also related to the severity and the duration of the disease and to the possible role of the MTHFR genotype (C677T).

METHOD

Plasma tHcy levels, homozygosity for the C677T mutation of the MTHFR gene, and folate and vitamin B(12) plasma levels were evaluated in 74 patients with AD (45 men, 29 women, mean age 68 years) and in 74 healthy matched controls (42 men, 32 women, mean age 68 years).

RESULTS

AD patients had higher mean (+/- SD) plasma levels of tHcy (20.9 +/- 15 micromol/l compared to 11.8 +/- 5 micromol/l, p < 0.001) and lower mean plasma folate (5.7 +/- 2.1 ng/ml compared to 8.5 +/- 3.2 ng/ml, p < 0.001) and vitamin B(12) (491 +/- 144 pmol/l compared to 780 +/- 211 pmol/l, p < 0.001) concentrations. Homozygosity for the C677T mutation of the MTHFR gene had a similar prevalence among controls (18%) and AD patients (20%). Homozygous AD patients (n = 15) had higher plasma tHcy values than nonhomozygotes, in spite of similar mean plasma folate and vitamin B(12) levels. This difference in plasma tHcy levels was not observed in controls. Patients with levels of plasma tHcy above and of plasma folate below the normal limits were more frequent in the homozygous AD group. The duration of the disease correlated with plasma levels of tHcy (r = +0.832, p < 0.001), plasma folate (r = -0.580, p < 0.05), and vitamin B(12) (r = -0.460, p < 0.05). However, when all the data were corrected for age, serum creatinine levels, and duration of the disease, mean plasma tHcy, folate, and vitamin B(12) levels were not statistically different between controls and AD patients.

CONCLUSIONS

Our data suggest that rather than a risk factor for AD, hyperhomocysteinemia is related to its progression and increasing severity. This might be particularly relevant in homozygotes for the C677T mutation of the MTHFR gene and supports the possible need for continuous supplements in this setting.

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  • Authors+Show Affiliations

    ,

    Department of Clinical and Experimental Medicine, University Federico II, Naples, Italy. alfposti@unina.it

    , , , ,

    Source

    Gerontology 47:6 pg 324-9

    MeSH

    Age Factors
    Aged
    Aged, 80 and over
    Alzheimer Disease
    Analysis of Variance
    Biomarkers
    Case-Control Studies
    Cohort Studies
    Female
    Folic Acid
    Genetic Markers
    Homocysteine
    Humans
    Logistic Models
    Male
    Methylenetetrahydrofolate Reductase (NADPH2)
    Oxidoreductases Acting on CH-NH Group Donors
    Point Mutation
    Probability
    Sensitivity and Specificity
    Severity of Illness Index
    Sex Factors
    Vitamin B 12

    Pub Type(s)

    Comparative Study
    Journal Article

    Language

    eng

    PubMed ID

    11721146

    Citation

    Postiglione, A, et al. "Plasma Folate, Vitamin B(12), and Total Homocysteine and Homozygosity for the C677T Mutation of the 5,10-methylene Tetrahydrofolate Reductase Gene in Patients With Alzheimer's Dementia. a Case-control Study." Gerontology, vol. 47, no. 6, 2001, pp. 324-9.
    Postiglione A, Milan G, Ruocco A, et al. Plasma folate, vitamin B(12), and total homocysteine and homozygosity for the C677T mutation of the 5,10-methylene tetrahydrofolate reductase gene in patients with Alzheimer's dementia. A case-control study. Gerontology. 2001;47(6):324-9.
    Postiglione, A., Milan, G., Ruocco, A., Gallotta, G., Guiotto, G., & Di Minno, G. (2001). Plasma folate, vitamin B(12), and total homocysteine and homozygosity for the C677T mutation of the 5,10-methylene tetrahydrofolate reductase gene in patients with Alzheimer's dementia. A case-control study. Gerontology, 47(6), pp. 324-9.
    Postiglione A, et al. Plasma Folate, Vitamin B(12), and Total Homocysteine and Homozygosity for the C677T Mutation of the 5,10-methylene Tetrahydrofolate Reductase Gene in Patients With Alzheimer's Dementia. a Case-control Study. Gerontology. 2001;47(6):324-9. PubMed PMID: 11721146.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Plasma folate, vitamin B(12), and total homocysteine and homozygosity for the C677T mutation of the 5,10-methylene tetrahydrofolate reductase gene in patients with Alzheimer's dementia. A case-control study. AU - Postiglione,A, AU - Milan,G, AU - Ruocco,A, AU - Gallotta,G, AU - Guiotto,G, AU - Di Minno,G, PY - 2001/11/27/pubmed PY - 2002/2/6/medline PY - 2001/11/27/entrez SP - 324 EP - 9 JF - Gerontology JO - Gerontology VL - 47 IS - 6 N2 - BACKGROUND: Elevated total plasma homocysteine (tHcy) levels are considered a risk factor for cerebrovascular disease and may also play an important role in the pathogenesis of Alzheimer's disease (AD). High values of plasma tHcy and low levels of vitamin B(12) and folate are frequently present in AD patients. Moreover, the homozygous mutation (C677T) of the methylene tetrahydrofolate reductase (MTHFR) gene, related to a thermolabile type of the encoded enzyme, causes hyperhomocysteinemia by reducing the 5-methyltetrahydrofolate availability. OBJECTIVE: The aim of the study was to investigate plasma levels of folate, vitamin B(12) and tHcy in patients with AD. These values were also related to the severity and the duration of the disease and to the possible role of the MTHFR genotype (C677T). METHOD: Plasma tHcy levels, homozygosity for the C677T mutation of the MTHFR gene, and folate and vitamin B(12) plasma levels were evaluated in 74 patients with AD (45 men, 29 women, mean age 68 years) and in 74 healthy matched controls (42 men, 32 women, mean age 68 years). RESULTS: AD patients had higher mean (+/- SD) plasma levels of tHcy (20.9 +/- 15 micromol/l compared to 11.8 +/- 5 micromol/l, p < 0.001) and lower mean plasma folate (5.7 +/- 2.1 ng/ml compared to 8.5 +/- 3.2 ng/ml, p < 0.001) and vitamin B(12) (491 +/- 144 pmol/l compared to 780 +/- 211 pmol/l, p < 0.001) concentrations. Homozygosity for the C677T mutation of the MTHFR gene had a similar prevalence among controls (18%) and AD patients (20%). Homozygous AD patients (n = 15) had higher plasma tHcy values than nonhomozygotes, in spite of similar mean plasma folate and vitamin B(12) levels. This difference in plasma tHcy levels was not observed in controls. Patients with levels of plasma tHcy above and of plasma folate below the normal limits were more frequent in the homozygous AD group. The duration of the disease correlated with plasma levels of tHcy (r = +0.832, p < 0.001), plasma folate (r = -0.580, p < 0.05), and vitamin B(12) (r = -0.460, p < 0.05). However, when all the data were corrected for age, serum creatinine levels, and duration of the disease, mean plasma tHcy, folate, and vitamin B(12) levels were not statistically different between controls and AD patients. CONCLUSIONS: Our data suggest that rather than a risk factor for AD, hyperhomocysteinemia is related to its progression and increasing severity. This might be particularly relevant in homozygotes for the C677T mutation of the MTHFR gene and supports the possible need for continuous supplements in this setting. SN - 0304-324X UR - https://www.unboundmedicine.com/medline/citation/11721146/Plasma_folate_vitamin_B_12__and_total_homocysteine_and_homozygosity_for_the_C677T_mutation_of_the_510_methylene_tetrahydrofolate_reductase_gene_in_patients_with_Alzheimer's_dementia__A_case_control_study_ L2 - https://www.karger.com?DOI=10.1159/000052822 DB - PRIME DP - Unbound Medicine ER -