Associations Between White Matter Lesions, Plasma Total Homocysteine and Methylenetetrahydrofolate Reductase Polymorphism in Alzheimer’s Disease

초록

Objective: To determine whether high plasma homocysteine levels and methylenetetrahydrofolate reductase (MTHFR) polymorphism are associated with white matter hyperintensities in AD. Background: Elevated plasma homocysteine levels are reported to be associated with an increased risk of Alzheimer’s disease (AD) and white matter hyperintensities on magnetic resonance imaging (MRI). White matter hyperintensities are common in AD patients on MRI. The pathogenesis of the increased risk of AD by hyperhomocysteinemia is still controversial. Design/Methods: Thirty outpatients with clinical diagnosis of probable AD (age, 72.8  6.7 years) were recruited. Plasma total homocysteine levels and MTHFR polymorphism were studied in the patients. Brains MRI were also taken. The scans were rated with the Age-Related White Matter Changes rating scale. Results: The mean total plasma homocysteine level of the AD patients was 11.7  5.1 mol/L. The mean score of white matter hyperintensities was 5.6 ± 4.5. The total plasma homocysteine levels were significantly correlated with the white matter hyperintensities (r = 0.37, p = 0.04). The six patients with MTHFR 677 TT genotype had higher total plasma homocyteine level (16.6 ± 9.2mol/L vs. 10.4 ± 3.0mol/L vs. 10.9 ± 2.5mol/L) and more severe white matter hyperintensities (8.3± 6.1 vs. 4.1 ± 3.4 vs. 5.4 ± 3.3) compared to those with MTHFR 677 CT or CC genotype. Conclusions/Relevance: Higher plasma total homocysteine level and MTHFR 677 TT polymorphism are associated with white matter hyperintensities in individuals with AD. The homocysteine might increase the risk of AD through ischemia by cerebrovascular injury.