TheMTHFR677T Allele May Influence the Severity and Biochemical Risk Factors of Alzheimer’s Disease in an Egyptian Population

Abstract

Objective. We evaluated whether the methylenetetrahydrofolate reductase (MTHFR) 677C>T marker influences the risk and severity of Alzheimer's disease (AD) and whether AD is associated with homocysteine, vitamin B12, and cholesterol levels in Egypt. Methods. Forty-three Alzheimer's cases and 32 non-AD controls were genotyped for the 677C>T polymorphism. Clinical characteristics and levels of homocysteine, vitamin B12, and cholesterol were assessed. Results. No significant differences in the frequencies of the MTHFR alleles or genotypes between AD cases and controls (P = 0.14) were identified. The 677T mutant allele was significantly overrepresented in AD cases compared to controls (OR = 2.22; P = 0.03). The 677T/T frequency was three times higher in AD patients than in controls, which could increase plasma homocysteine levels. Severe cases of AD were the most frequent in patients with the T/T genotype (11.6%). The effect of the MTHFR polymorphism on the risk of AD may be independent of homocysteine, vitamin B12, or even cholesterol levels. Conclusions. The MTHFR 677C>T polymorphism—especially the presence of one copy of the T allele—appears to confer a potential risk for the development of AD. The T/T genotype may contribute to hypercysteinemia as a sensitive marker.

Nutritional supplementation for Alzheimerʼs disease?

“…Folate, B12 and SAM are components of onecarbon metabolism (the so-called 'methionine cycle'); methylation events mediated by this cycle play a critical role in neuronal homeostasis throughout life, and impaired function of this cycle is associated with Alzheimer's disease [2 & ,52,65,66]. However, the C677T was not associated with cognitive problems in adults receiving adequate folate [68][69][70][71][72][73]. PSEN-1, the gene that codes for presenilin, is particularly susceptible to overexpression following hypomethylation, which sets of a cascade leading to beta-secretase and gamma-secretase overactivation and generation of increased Abeta.…”

Homocysteine-Induced Endothelial Dysfunction

“…Hyperhomocysteinemia is defined as a pathological condition of excessive plasma homocysteine level (normal homocysteine levels ranges from 4 to 12.3 μmol/l) [1]. In 1969, when children with homocysteinuria were observed to have a high susceptibility to premature death due to severe atherosclerosis and thrombotic occlusions, McCully et al [2 ]proposed the notion of hyperhomocysteinemia as an independent cardiovascular risk factor.…”

The C677T polymorphism of the methylenetetrahydrofolate reductase gene and susceptibility to late-onset Alzheimer’s disease

“…As evident from Figure 1, an aggregate of 343 articles was recognized in the preliminary search in PubMed, EMBASE, the Cochrane Library, as well as WanFang databases. Subsequent to the deduplication and exclusion of the clearly irrelevant studies, an aggregate of 14 case-control research works was retrieved, which involved 2,467 LOAD patients with 2,877 controls [14, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35]. Key attributes of individual investigations are summarized in Table 1.…”