Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
1993; Lippincott Williams & Wilkins; Volume: 43; Issue: 8 Linguagem: Inglês
10.1212/wnl.43.8.1467
ISSN1526-632X
AutoresAnn M. Saunders, Warren J. Strittmatter, D. E. Schmechel, Peter St George‐Hyslop, Jeffery M. Vance, Sun Hyung Joo, B.L. Rosi, James F. Gusella, D. R. Crapper-MacLachlan, Mark J. Alberts, Christine Hulette, Barbara J. Crain, Dmitry Goldgaber, Allen D. Roses,
Tópico(s)Dementia and Cognitive Impairment Research
ResumoApolipoprotein E, type ϵ4 allele (APOE ϵ4), is associated with late-onset familial Alzheimer9s disease (AD). There is high avidity and specific binding of amyloid β-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 ϵ4 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 d9Etude 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 ϵ4 allele (0.40 ± 0.026, p ≤ 0.00001). These data support the involvement of ApoE ϵ4 in the pathogenesis of late-onset familial and sporadic AD. ApoE isoforms may play an important role in the metabolism of β-peptide, and APOE ϵ4 may operate as a susceptibility gene (risk factor) for the clinical expression of AD.
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