ASSOCIATION OF APOLIPOPROTEIN-E ALLELE EPSILON-4 WITH LATE-ONSET FAMILIAL AND SPORADIC ALZHEIMERS-DISEASE

Apolipoprotein E, type epsilon4 allele (APOE epsilon4), is associated with late-onset familial Alzheimer's disease (AD). There is high avidity and specific binding of amyloid beta-peptide with the protein ApoE. To test the hypothesis that late-onset familial AD may represent the clustering of sporadic AD in families large enough to be studied, we extended the analyses of APOE alleles to several series of sporadic AD patients. APOE epsilon4 is significantly associated with a series of probable sporadic AD patients (0.36 +/- 0.042, AD, versus 0.16 +/- 0.027, controls [allele frequency estimate +/-standard error], p = 0.00031). Spouse controls did not differ from CEPH grandparent controls from the Centre d'Etude du Polymorphisme Humain (CEPH) or from literature controls. A large combined series of autopsy-documented sporadic AD patients also demonstrated highly significant association with the APOE epsilon4 allele (0.40 +/- 0.026, p less-than-or-equal-to 0.00001). These data support the involvement of ApoE epsilon4 in the pathogenesis of late-onset familial and sporadic AD. ApoE isoforms may play an important role in the metabolism of beta-peptide, and APOE epsilon4 may operate as a susceptibility gene (risk factor) for the clinical expression of AD.