Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease

@article{Corder1994ProtectiveEO,
  title={Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease},
  author={Elizabeth H. Corder and Ann M Saunders and Neil Risch and Warren J. Strittmatter and Detlef Schmechel and Peter C. Gaskell and Jackie B. Rimmler and P. A. Locke and P. Michael Conneally and Kenneth E. Schmader and Gary W. Small and Allen D. Roses and Jonathan L. Haines and Margaret A. Pericak-Vance},
  journal={Nature Genetics},
  year={1994},
  volume={7},
  pages={180-184}
}
Gene dosage of the apolipoprotein E (APOE) ε4 allele is a major risk factor for familial Alzheimer disease (AD) of late onset (after age 60). Here we studied a large series of 115 AD case subjects and 243 controls as well as 150 affected and 197 unaffected members of 66 AD families. Our data demonstrate a protective effect of the ε2 allele, in addition to the dose effect of the ε4 allele in sporadic AD. Although a substantial proportion (65%) of AD is attributable to the presence of ε4 alleles… 
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In vitro and animal model studies strongly suggest that brain apolipoprotein E is a multifunctional molecule, with potential roles in amyloid deposition and clearance, microtubule stability, intracellular signaling, immune modulation, glucose metabolism, oxidative stress, and other cellular processes.
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The data show that among EOAD patients, survival for APOE*2 carriers was significantly reduced, and when restricting the analysis to patients ascertained early after diagnosis at a stage of disease when mortality is low, the data suggest an increased risk of EOAD for subjects with APOE2E2, APoe2E3, APOE3E4, and APOE4E4 genotypes.
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It is concluded, contrary to some previous reprots, that the ApoE ε2 allele does not increase the risk of early‐onset sporadic AD.
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TLDR
The data suggest that the relation of the apoE genotype to AD is not dependent on sex and the odds ratio for AD, when associated with 1 or 2 4 alleles, were not statistically different between men and women.
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TLDR
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Apolipoprotein E and ALzheimer's Disease: The Tip of the Susceptibility Iceberg
  • A. Roses
  • Biology
    Annals of the New York Academy of Sciences
  • 1998
TLDR
With the anticipation of a second major late‐onset AD susceptibility locus on chromosome 12, a matrix of relative susceptibility risks in the population raises many ethical and social questions associated with preclinical prediction.
The Neurobiology and Age-Related Prevalence of the ε4 Allele of Apolipoprotein E in Alzheimer’s Disease Cohorts
TLDR
First data on age-related prevalence of APOE ε4 in AD in three AD cohorts in Australia and the USA is presented, showing a significant association between age and ε 4 prevalence, particularly forε4 homozygotes, such that as age increases the prevalence of ε3 decreases.
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TLDR
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