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The apolipoprotein E4 (apoE4) epsilon 4 allele is a major riks factor for Alzheimer's disease. However, epsilon 4 is neither a necessary nor a sufficient condition for the development of this disease, and many cognitively healthy elderly people carry the epsilon 4 allele. To look for age-dependent changes in epsilon 4 allele frequencies in the general population, we measured the frequencies in 141 normal healthy residents of a mountainous rural area in north-west Gunma prefecture. Levels of cholesterols in plasma were measured and their relation to apoE genotypes was studied. We also measured the levels of alpha 2-macroglobulin (alpha 2M) and plasminogen activator inhibitor 1 (PAI-1) in blood, and studied their relation to apoE genotypes. Because low-density lipoprotein receptor-related protein (LRP) binds apoE, alpha 2M, and PAI-1, it is of interest to see whether the alpha 2M and PAI-1 concentrations in blood differ between epsilon 4 carriers and non-carriers. ApoE allele frequencies were 0.05, 0.84, and 0.11 for epsilon 2, epsilon 3, and epsilon 4, respectively. In both men and women, the frequency of epsilon 4 was lowest among those in the seventh decade of life. The frequency of epsilon 4 among octagenarians was high (0.17). Serum levels of total cholesterol and low-density lipoprotein cholesterol did not differ significantly between epsilon 4 carriers and non-carriers. The alpha 2M level in serum was higher in women than in men and was higher in older subjects than in younger subjects. Plasma PAI-1 levels were significantly higher in men than in women (Student's t-test, p = 0.0197). Neither alpha 2M levels nor PAI-1 levels differed between epsilon 4 carriers and non-carriers, which suggests that the levels of these two proteins in blood do not reflect the status of LRP in individuals with various apoE genotypes. Studies that include data on life style and diet are necessary before we can conclude that rural life contributes to longevity in epsilon 4 carriers.

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Apolipoprotein E.EPSILON.4 Allel Frequencies, Plasma .ALPHA.2-Macroglobulin and Plasminogen Activator Inhibitor 1 Levels in Residents of a Rural Area in Gunma Prefecture.