Apolipoprotein E genotype in sporadic early- and late-onset Alzheimer's disease

The epsilon 4 isoform of apolipoprotein E (ApoE) has been proposed as a risk factor for Alzheimer's disease (AD), while the possible role of the epsilon 2 allele in AD is controversial. We have studied the ApoE genotype in 38 patients with early-onset AD (EOAD) and in 43 patients with late-onset AD (LOAD). In the LOAD group we observed a significant increase of epsilon 4 allele frequency as compared with normal controls, while there was a more than 3-fold decrease of epsilon 2 allele frequency that did not reach statistical significance. In the LOAD group we found a highly significant increase of epsilon 4 allele frequency as compared with normal controls, while there was a significant decrease of epsilon 2 allele frequency. In both the EOAD and LOAD groups, no significant difference was observed between epsilon 4 carriers and epsilon 4 noncarriers as for age at disease onset, disease duration, and Mini-Mental State score at observation. However, in both EOAD and LOAD groups a statistical trend towards a longer disease duration was observed in epsilon 4 carriers. In both the EOAD and LOAD groups, disease severity was compared in epsilon 4 carriers versus epsilon 4 noncarriers by means of analyses of covariance, with disease duration as covariate. No significant difference between epsilon 4 carriers and epsilon 4 noncarriers was observed in both EOAD and LOAD. The results of the present study confirm that epsilon 4 allele seems to be associated with an increased risk for sporadic AD, while the significant decrease of epsilon 2 allele frequency in the LOAD group supports the hypothesis of a possible protective role of epsilon 2 allele in AD.