Association of apolipoprotein E allele ∈4 with late-onset familial and sporadic Alzheimer's disease

A. M. Saunders, W. J. Strittmatter, D. Schmechel, P. H. St. George-Hyslop, M. A. Pericak-Vance, S. H. Joo, B. L. Rosi, J. F. Gusella, D. R. Crapper-MacLachlan, M. J. Alberts, C. Hulette, B. Crain, D. Goldgaber, A. D. Roses

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Abstract

Apolipoprotein E, type ∈4 allele (APOE ∈4), 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 ∈4 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 ∈4 allele (0.40 ± 0.026, p < 0.00001). These data support the involvement of ApoE ∈4 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 ∈4 may operate as a susceptibility gene (risk factor) for the clinical expression of AD.

Original languageEnglish (US)
Pages (from-to)1467-1472
Number of pages6
JournalNeurology
Volume43
Issue number8
StatePublished - Aug 1993

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Apolipoprotein E4
Alzheimer Disease
Alleles
Apolipoproteins E
Spouses
Amyloid
Gene Frequency
Cluster Analysis
Alzheimer disease type 2
Autopsy
Protein Isoforms
Peptides
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., ... Roses, A. D. (1993). Association of apolipoprotein E allele ∈4 with late-onset familial and sporadic Alzheimer's disease. Neurology, 43(8), 1467-1472.

Association of apolipoprotein E allele ∈4 with late-onset familial and sporadic Alzheimer's disease. / Saunders, A. M.; Strittmatter, W. J.; Schmechel, D.; St. George-Hyslop, P. H.; Pericak-Vance, M. A.; Joo, S. H.; Rosi, B. L.; Gusella, J. F.; Crapper-MacLachlan, D. R.; Alberts, M. J.; Hulette, C.; Crain, B.; Goldgaber, D.; Roses, A. D.

In: Neurology, Vol. 43, No. 8, 08.1993, p. 1467-1472.

Research output: Contribution to journalArticle

Saunders, AM, Strittmatter, WJ, Schmechel, D, St. George-Hyslop, PH, Pericak-Vance, MA, Joo, SH, Rosi, BL, Gusella, JF, Crapper-MacLachlan, DR, Alberts, MJ, Hulette, C, Crain, B, Goldgaber, D & Roses, AD 1993, 'Association of apolipoprotein E allele ∈4 with late-onset familial and sporadic Alzheimer's disease', Neurology, vol. 43, no. 8, pp. 1467-1472.
Saunders AM, Strittmatter WJ, Schmechel D, St. George-Hyslop PH, Pericak-Vance MA, Joo SH et al. Association of apolipoprotein E allele ∈4 with late-onset familial and sporadic Alzheimer's disease. Neurology. 1993 Aug;43(8):1467-1472.
Saunders, A. M. ; Strittmatter, W. J. ; Schmechel, D. ; St. George-Hyslop, P. H. ; Pericak-Vance, M. A. ; Joo, S. H. ; Rosi, B. L. ; Gusella, J. F. ; Crapper-MacLachlan, D. R. ; Alberts, M. J. ; Hulette, C. ; Crain, B. ; Goldgaber, D. ; Roses, A. D. / Association of apolipoprotein E allele ∈4 with late-onset familial and sporadic Alzheimer's disease. In: Neurology. 1993 ; Vol. 43, No. 8. pp. 1467-1472.
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