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Abstract

Apolipoprotein E, type ϵ4 allele (APOE ϵ4), is associated with late-onset familial Alzheimer's 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 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 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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Published In

Neurology®
Volume 43Number 8August 1993
Pages: 1467
PubMed: 8350998

Publication History

Published online: August 1, 1993
Published in print: August 1993

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Authors

Affiliations & Disclosures

A. M. Saunders, PhD
Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; the Department of Neurology (Dr. Gusella), Massachusetts General Hospital, Boston, MA, and the Department of Psychiatry (Dr. Goldgaber), State University of New York at Stony Brook, Stony Brook, NY.
W. J. Strittmatter, MD
Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; the Department of Neurology (Dr. Gusella), Massachusetts General Hospital, Boston, MA, and the Department of Psychiatry (Dr. Goldgaber), State University of New York at Stony Brook, Stony Brook, NY.
D. Schmechel, MD
Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; the Department of Neurology (Dr. Gusella), Massachusetts General Hospital, Boston, MA, and the Department of Psychiatry (Dr. Goldgaber), State University of New York at Stony Brook, Stony Brook, NY.
P. H. St. George-Hyslop, MD
Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; the Department of Neurology (Dr. Gusella), Massachusetts General Hospital, Boston, MA, and the Department of Psychiatry (Dr. Goldgaber), State University of New York at Stony Brook, Stony Brook, NY.
M. A. Pericak-Vance, PhD
Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; the Department of Neurology (Dr. Gusella), Massachusetts General Hospital, Boston, MA, and the Department of Psychiatry (Dr. Goldgaber), State University of New York at Stony Brook, Stony Brook, NY.
S. H. Joo, BS
Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; the Department of Neurology (Dr. Gusella), Massachusetts General Hospital, Boston, MA, and the Department of Psychiatry (Dr. Goldgaber), State University of New York at Stony Brook, Stony Brook, NY.
B. L. Rosi, BA
Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; the Department of Neurology (Dr. Gusella), Massachusetts General Hospital, Boston, MA, and the Department of Psychiatry (Dr. Goldgaber), State University of New York at Stony Brook, Stony Brook, NY.
J. F. Gusella, PhD
Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; the Department of Neurology (Dr. Gusella), Massachusetts General Hospital, Boston, MA, and the Department of Psychiatry (Dr. Goldgaber), State University of New York at Stony Brook, Stony Brook, NY.
D. R. Crapper-MacLachlan, MD
Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; the Department of Neurology (Dr. Gusella), Massachusetts General Hospital, Boston, MA, and the Department of Psychiatry (Dr. Goldgaber), State University of New York at Stony Brook, Stony Brook, NY.
M. J. Alberts, MD
Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; the Department of Neurology (Dr. Gusella), Massachusetts General Hospital, Boston, MA, and the Department of Psychiatry (Dr. Goldgaber), State University of New York at Stony Brook, Stony Brook, NY.
C. Hulette, MD
Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; the Department of Neurology (Dr. Gusella), Massachusetts General Hospital, Boston, MA, and the Department of Psychiatry (Dr. Goldgaber), State University of New York at Stony Brook, Stony Brook, NY.
B. Crain, MD
Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; the Department of Neurology (Dr. Gusella), Massachusetts General Hospital, Boston, MA, and the Department of Psychiatry (Dr. Goldgaber), State University of New York at Stony Brook, Stony Brook, NY.
D. Goldgaber, PhD
Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; the Department of Neurology (Dr. Gusella), Massachusetts General Hospital, Boston, MA, and the Department of Psychiatry (Dr. Goldgaber), State University of New York at Stony Brook, Stony Brook, NY.
A. D. Roses, MD
Departments of Medicine [Neurology] (Drs. Saunders, Strittmatter, Schmechel, Pericak-Vance, Alberts, and Roses, and S. Joo and B. Rosi), Neurobiology (Drs. Strittmatter, Schmechel, and Roses), and Pathology (Drs. Hulette and Crain), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC; the Department of Medicine [Neurology] (Drs. St. George-Hyslop and Crapper-MacLachlan), Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; the Department of Neurology (Dr. Gusella), Massachusetts General Hospital, Boston, MA, and the Department of Psychiatry (Dr. Goldgaber), State University of New York at Stony Brook, Stony Brook, NY.

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