Apolipoprotein E phenotypes in healthy normal controls and demented subjects with Alzheimer's disease and vascular dementia in Mie Prefecture of Japan

In order to clarify the association between apolipoprotein E4 (ApoE4) and t he pathogenesis of Alzheimer's disease (AD), we analyzed the distribution o f the apolipoprotein E (ApoE) phenotypes and the frequency of the apo E all eles epsilon 2, epsilon 3, and epsilon 4 in Japanese healthy controls (n = 1090, an average age of 51.2 +/- 12.6 years) and demented patients (n = 103 , mean age of 73.6 +/- 9.2 years). Demented subjects were divided into thre e subgroups: early-onset AD group (EOAD; n = 25, mean age 63.0+/-6.2 years) , late-onset AD group (LOAD; n = 33, mean age 79.3 +/- 5.1 years), and vasc ular dementia group (VD; n = 45, mean age 75.3+/-8.0 years). The apolipopro tein E phenotype was determined by isoelectric focusing and immunoblotting. There were no significant differences in the distribution of the apo E phe notypes by gender or age, and the estimated frequencies of epsilon 2, epsil on 3 and epsilon 4 were 0.05, 0.86 and 0.09, respectively, in the normal co ntrols. There was a significant difference in the distribution off the apo E phenotypes between LOAD and elderly controls aged more than 65 years (P < 0.0001). The distribution of the apo E phenotypes in LOAD was the same as that in LOAD. The frequency of the E4 allele was significantly higher in LO AD (0.35, P < 0.0001) and EOAD (0.28, P < 0.0001) than that in the control subjects (0.07), but not in VD (0.12, P = 0.1630). The present findings sug gest that ApoE4 is related with both EOAD and LOAD, but not with VD, and su pport the hypothesis that it is a genetic risk factor of AD.