In order to prevent Alzheimer disease (AD), relationship between single nucleotide polymorphisms (SNPs) of methylene tetrahydrofolate reductase (MTHFR) and folate-homocysteine metabolism was studied. Subjects were 10 males and 42 females (87.9 +/- 7.7 years old) in the special nursing homes for the elderly. Their average care level was 4.2 +/- 0.9, and average cognitive ability estimated by MMSE was 6.9 +/-7.3. Dietary intake was measured by weighing method. Concentrations of serum folate and total serum homocysteine (tHcy), and genetic polymorphisms were determined. The daily nutrient intake was as follows: total energy 2.7 kcal/kg; protein, 1.0 g/kg; folic acid, 7.3 microg/kg; vitamin B12, 0.11 microg/kg. Compared with control elderly persons, serum folate was very low (4.5 ng/ml, control = 10.1 ng/ml) and serum homocysteine was very high (21.4 micromol/L, control = 10.2 microg/L), despite having an adequate folate intake (342 microg/day, mainly polyglutamyl folate). The frequency of TT homozygote of MTHFR was higher (21.1%) in Alzheimer patients than that in control (15%). TT homozygotes showed the lowest serum folate (3.5 ng/ml, 35% of control), the highest serum homocysteine 25 micromol/L, 250% of control and the lowest MMSE score (5) among all the genotypes. The bioavailability of polyglutamyl folate may be impaired in the subjects, even when their total folate intake was sufficient. The early prevention of Alzheimer's disease by monoglutamyl folate intake (400 mcg per day) is recommended especially in TT homozygote of MTHFR.