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Apolipoprotein E epsilon4 count affects age at onset of Alzheimer disease, but not lifetime susceptibility: The Cache County Study.

Abstract

BACKGROUND

The incidence of Alzheimer disease (AD) increases strongly with age, but little is known about the cumulative incidence of AD over a lifetime of 100 years, or its relationship to the polymorphic APOE locus that encodes apolipoprotein E. APOE is a strong genetic risk factor for AD.

OBJECTIVES

To estimate the occurrence of AD as a function of age and number of APOE epsilon4 alleles; and to explore evidence for heterogeneity of AD risk related to APOE genotype and to other sources.

DESIGN

Nonparametric and parametric survival analyses of AD incidence in prospective longitudinal study.

SETTING AND PARTICIPANTS

A total of 3308 elderly residents of Cache County, Utah.

MAIN OUTCOME MEASURES

Cumulative incidence of AD; in mixture models assuming susceptible and nonsusceptible individuals, the proportion of individuals not susceptible to AD at any age.

RESULTS

Models that assumed a proportion of invulnerable individuals provided strongly improved fit to the data. These models estimated the 100-year lifetime incidence of AD at 72%, implying that 28% of individuals would not develop AD over any reasonable life expectancy. We confirmed the acceleration of AD onset in individuals with 1 or, especially, 2 APOE, epsilon4 alleles but observed no meaningful difference in 100-year lifetime incidence related to number of epsilon4 alleles.

CONCLUSIONS

The APOE epsilon4 allele acts as a potent risk factor for AD by accelerating onset. However, the risk of AD appears heterogeneous in ways independent of APOE. Some individuals seem destined to escape AD, even over an extended lifespan. Their relative invulnerability may reflect other genes or environmental factors that can be investigated.

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  • Authors+Show Affiliations

    ,

    Khachaturian and Associates Inc, Potomac, MD, USA.

    , , , ,

    Source

    Archives of general psychiatry 61:5 2004 May pg 518-24

    MeSH

    Age of Onset
    Aged
    Aged, 80 and over
    Aging
    Alzheimer Disease
    Apolipoprotein E4
    Apolipoproteins E
    Female
    Genetic Heterogeneity
    Genetic Predisposition to Disease
    Genotype
    Humans
    Incidence
    Longitudinal Studies
    Male
    Prospective Studies
    Risk Factors
    Survival Analysis
    Utah

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    15123497

    Citation

    Khachaturian, Ara S., et al. "Apolipoprotein E Epsilon4 Count Affects Age at Onset of Alzheimer Disease, but Not Lifetime Susceptibility: the Cache County Study." Archives of General Psychiatry, vol. 61, no. 5, 2004, pp. 518-24.
    Khachaturian AS, Corcoran CD, Mayer LS, et al. Apolipoprotein E epsilon4 count affects age at onset of Alzheimer disease, but not lifetime susceptibility: The Cache County Study. Arch Gen Psychiatry. 2004;61(5):518-24.
    Khachaturian, A. S., Corcoran, C. D., Mayer, L. S., Zandi, P. P., & Breitner, J. C. (2004). Apolipoprotein E epsilon4 count affects age at onset of Alzheimer disease, but not lifetime susceptibility: The Cache County Study. Archives of General Psychiatry, 61(5), pp. 518-24.
    Khachaturian AS, et al. Apolipoprotein E Epsilon4 Count Affects Age at Onset of Alzheimer Disease, but Not Lifetime Susceptibility: the Cache County Study. Arch Gen Psychiatry. 2004;61(5):518-24. PubMed PMID: 15123497.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Apolipoprotein E epsilon4 count affects age at onset of Alzheimer disease, but not lifetime susceptibility: The Cache County Study. AU - Khachaturian,Ara S, AU - Corcoran,Christopher D, AU - Mayer,Lawrence S, AU - Zandi,Peter P, AU - Breitner,John C S, AU - ,, PY - 2004/5/5/pubmed PY - 2004/5/27/medline PY - 2004/5/5/entrez SP - 518 EP - 24 JF - Archives of general psychiatry JO - Arch. Gen. Psychiatry VL - 61 IS - 5 N2 - BACKGROUND: The incidence of Alzheimer disease (AD) increases strongly with age, but little is known about the cumulative incidence of AD over a lifetime of 100 years, or its relationship to the polymorphic APOE locus that encodes apolipoprotein E. APOE is a strong genetic risk factor for AD. OBJECTIVES: To estimate the occurrence of AD as a function of age and number of APOE epsilon4 alleles; and to explore evidence for heterogeneity of AD risk related to APOE genotype and to other sources. DESIGN: Nonparametric and parametric survival analyses of AD incidence in prospective longitudinal study. SETTING AND PARTICIPANTS: A total of 3308 elderly residents of Cache County, Utah. MAIN OUTCOME MEASURES: Cumulative incidence of AD; in mixture models assuming susceptible and nonsusceptible individuals, the proportion of individuals not susceptible to AD at any age. RESULTS: Models that assumed a proportion of invulnerable individuals provided strongly improved fit to the data. These models estimated the 100-year lifetime incidence of AD at 72%, implying that 28% of individuals would not develop AD over any reasonable life expectancy. We confirmed the acceleration of AD onset in individuals with 1 or, especially, 2 APOE, epsilon4 alleles but observed no meaningful difference in 100-year lifetime incidence related to number of epsilon4 alleles. CONCLUSIONS: The APOE epsilon4 allele acts as a potent risk factor for AD by accelerating onset. However, the risk of AD appears heterogeneous in ways independent of APOE. Some individuals seem destined to escape AD, even over an extended lifespan. Their relative invulnerability may reflect other genes or environmental factors that can be investigated. SN - 0003-990X UR - https://www.unboundmedicine.com/medline/citation/15123497/Apolipoprotein_E_epsilon4_count_affects_age_at_onset_of_Alzheimer_disease_but_not_lifetime_susceptibility:_The_Cache_County_Study_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=15123497.ui DB - PRIME DP - Unbound Medicine ER -