Apolipoprotein E Genotype Determines Survival in the Oldest Old (85 Years or Older) Who Have Good Cognition

Corder, Elizabeth H.; Lannfelt, Lars; Viitanen, Matti; Corder, Larry S.; Mantón, Kenneth G.; Winblad, Bengt; Basun, Hans

doi:10.1001/archneur.1996.00550050048022

Cited by 116 publications

(94 citation statements)

References 33 publications

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“…Age is the most important risk factor for AD, but surprisingly, apoE4 genotype impacts cognition even in healthy, non-demented, and young individuals (9,10). Also, whereas longitudinal cognitive decline is steeper in apoE4 carriers (11,12,68), numerous reports have shown that the effect of apoE4 on cognition is actually greater in younger than in older subjects (45)(46)(47). Thus, our results showing cognitive deficits in young Arg-61 mice are consistent with the apoE4 cognitive phenotype hypothesis (69).…”

Section: Discussionsupporting

confidence: 87%

“…This is in contrast to detectable deficits on the first day training in 3-month-old mice. As further discussed below, although, apoE4-like domain interaction negatively impact learning and memory in old mice, it seemed that the effect of apoE4 on cognition wane with age as concluded in several human studies (45)(46)(47). This does not contradict the fact that age and apoE4 gene are the top two risk factors for AD and, therefore, should interact to amplify the risk; it only means that even though the risk of developing AD increases with age, the presence of apoE4 increases the risk more at younger ages than it does at older ages.…”

Section: Discussionmentioning

confidence: 82%

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Cognitive Deficits and Disruption of Neurogenesis in a Mouse Model of Apolipoprotein E4 Domain Interaction

Adeosun

Hou

Zheng

et al. 2014

Journal of Biological Chemistry

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Background: Domain interaction may be the principal pathogenic feature of apoE4 in Alzheimer disease. Results: Young and old mice with mutations causing apoE4 domain interaction showed impaired cognition and a disruption in neurogenesis. Conclusion: Domain interaction mediates apoE4 neuro-pathologies and cognitive phenotype. Significance: Domain interaction is a viable prophylactic target against apoE4 cognitive phenotype and increased susceptibility to Alzheimer disease.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 82%

Cognitive Deficits and Disruption of Neurogenesis in a Mouse Model of Apolipoprotein E4 Domain Interaction

Adeosun

Hou

Zheng

et al. 2014

Journal of Biological Chemistry

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“…Corder et al (31) quantified the influence of APOE on survival in a population sample of 1077 subjects aged 75 or older. The main results of this investigation were: 1) The mortality of subjects with the APOE*2/ E*3 genotype was half that of subjects who carried the APOE*3/E*3 genotype.…”

Section: Discussionmentioning

confidence: 99%

Association of apolipoprotein E polymorphism with plasma lipids and Alzheimer's disease in a Southern Brazilian population

de-Andrade

Larrandaburu

Callegari-Jacques

et al. 2000

Braz J Med Biol Res

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Apolipoprotein E (protein: apo E; gene: APOE) plays an important role in the multifactorial etiology of both Alzheimers disease (AD) and lipid level concentrations. The polymerase chain reaction (PCR) was used to investigate the APOE gene polymorphism in 446 unrelated Caucasians, among them 23 AD patients, and 100 Afro-Brazilians living in Porto Alegre, Brazil. The frequencies of the APOE*2, APOE*3 and APOE*4 alleles were 0.075, 0.810 and 0.115 in Caucasians and 0.075, 0.700 and 0.225 in Afro-Brazilians, respectively (c 2 = 8.72, P = 0.013). A highly significant association was observed between the APOE*4 allele and AD in this population-based sample. The APOE*4 frequency in AD patients (39%) was about four times higher than in the general Caucasian population (11.5%). The influence of each of the three common APOE alleles on lipid traits was evaluated by the use of the average excess statistic. The E*2 allele is associated with lower levels of triglycerides and of total and non-HDL cholesterol in both men and women. Conversely, the E*4 allele is associated with higher levels of these traits in women only. The effect of APOE alleles was of greater magnitude in women.

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“…Schacter et al and Louhija et al have found smaller frequencies of the ApoE ε4 allele in French and Finnish centenarians compared to younger cohorts, suggesting an increased mortality with ApoE ε4 [11,16]. Corder et al found in subjects 75-85 years old with and without cognitive impairment and cognitively impaired subjects 85 years or older that ApoE did not significantly predict survival, while among 85 year or older subjects with good cognition, mortality increased with a ε3/ε4 genotype and decreased with an ε2/ε3 genotype relative to the ε3/ε3 genotype [1]. Tilvis et al found that the presence of the ApoE ε4 allele was associated with 5-year mortality in 75 and 80 year old Finish subjects but not with 85 year old subjects [18].…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E and mortality in African-Americans and Yoruba

Lane

Gao

Hui

et al. 2003

JAD

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The literature on the association between apolipoprotein E (ApoE) and mortality across ethnic and age groups has been inconsistent. No studies have looked at this association in developing countries. We used data from the Indianapolis-Ibadan Dementia study to examine this association between APOE and mortality in 354 African-Americans from Indianapolis and 968 Yoruba from Ibadan, Nigeria. Participants were followed up to 9.5 years for Indianapolis and 8.7 years for Ibadan. Subjects from both sites were divided into 2 groups based upon age at baseline. A Cox proportional hazards regression model adjusting for age at baseline, education, hypertension, smoking history and gender in addition to time-dependent covariates of cancer, diabetes, heart disease, stroke, and dementia was fit for each cohort and age group. Having ApoE ε4 alleles significantly increased mortality risk in Indianapolis subjects under age 75 ( hazard ratio: 2.00; 95% CI: 1.19-3.35; p = 0.0089). No association was found in Indianapolis subjects 75 and older (hazard ratio: 0.71; 95% CI: 0.45-1.10; p = 0.1238), Ibadan subjects under 75 (hazard ratio: 1.04; 95% CI: 0.78 to 1.40; p = 0.7782), or Ibadan subjects over 75 (hazard ratio: 1.21; 95% CI: 0.83 to 1.75; p = 0.3274).

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Apolipoprotein E Genotype Determines Survival in the Oldest Old (85 Years or Older) Who Have Good Cognition

Cited by 116 publications

References 33 publications

Cognitive Deficits and Disruption of Neurogenesis in a Mouse Model of Apolipoprotein E4 Domain Interaction

Cognitive Deficits and Disruption of Neurogenesis in a Mouse Model of Apolipoprotein E4 Domain Interaction

Association of apolipoprotein E polymorphism with plasma lipids and Alzheimer's disease in a Southern Brazilian population

Apolipoprotein E and mortality in African-Americans and Yoruba

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