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 avidi ty 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 e xtended the analyses of APOE alleles to several series of sporadic AD patients. APOE epsilon4 is significantly associated with a series of p robable sporadic AD patients (0.36 +/- 0.042, AD, versus 0.16 +/- 0.02 7, 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 c ontrols. A large combined series of autopsy-documented sporadic AD pat ients also demonstrated highly significant association with the APOE e psilon4 allele (0.40 +/- 0.026, p less-than-or-equal-to 0.00001). Thes e data support the involvement of ApoE epsilon4 in the pathogenesis of late-onset familial and sporadic AD. ApoE isoforms may play an import ant role in the metabolism of beta-peptide, and APOE epsilon4 may oper ate as a susceptibility gene (risk factor) for the clinical expression of AD.