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 ( ) were identified. The 677T mutant allele was significantly overrepresented in AD cases compared to controls ( ; ). 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. 1. Introduction Alzheimer’s disease (AD, MIM 104300) is a major cause of disability in the elderly population. It is the most common form of dementia, affecting 1 in 8 individuals older than 60 years of age [1]. Most AD cases are late in onset and are probably influenced by both genetic and environmental factors. Clinically, AD generally begins with subtle short-term memory problems and then progresses to difficulties in memory, language, and orientation. In the late stage of AD, ventricular enlargement and shrinkage of the brain may be observed by magnetic resonance imaging. Some characteristic changes in the AD brain include neuronal loss in selected regions; intracellular neurofibrillary tangles in the neurons of the cerebral cortex and hippocampus; and neuritic plaques containing amyloids that may be further surrounded by dystrophic neurites, reactive astrocytes, and microglia [1]. Alzheimer Disease International estimates that there are currently 30 million cases of dementia in the world, with 4.6 million new cases occurring annually [2]. Statistics is much more ambiguous in the developing world, where few studies have examined the prevalence of dementia and where estimates vary widely. Evidence on the prevalence of AD is abundant in Europe and North America, patchy in South and Southeast Asia, and very
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