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Apolipoprotein E epsilon4 and age at onset of sporadic and familial Alzheimer disease in Caribbean Hispanics.

Abstract

BACKGROUND

The primary effect of the apolipoprotein E epsilon4 (APOE epsilon4) allele is on the age at onset of Alzheimer disease (AD).

OBJECTIVE

To investigate whether the presence of the APOE epsilon4 allele can account for the earlier age at onset of familial AD (FAD) compared with sporadic AD (SAD).

DESIGN

Population-based, case series ascertained in a prospective study of aging and dementia in Medicare recipients aged 65 years or older.

SETTING

Clinics in northern Manhattan and in the Dominican Republic and Puerto Rico.

PARTICIPANTS

There were 680 Caribbean Hispanic subjects: 111 patients with FAD, with at least 1 family member with dementia; 163 patients with SAD; and 406 elderly persons without dementia or other illnesses. Main Outcome Measure Age at onset of dementia was examined in relation to frequency of APOE epsilon4. Sex, education, and medical risk factors for stroke, hypertension, diabetes, and heart disease were examined as effect modifiers.

RESULTS

The mean age at onset of AD was significantly lower in FAD than in SAD, and a statistically significant dose effect of the APOE epsilon4 allele was present for age at onset in FAD (P = .001) but not in SAD. The age at onset in patients homozygous for the APOE epsilon4 allele with FAD and SAD was similar. Compared with SAD, the major difference was younger age at onset in patients with FAD who were heterozygous for the APOE epsilon4 allele and those without an APOE epsilon4 allele.

CONCLUSIONS

Apolipoprotein E epsilon4 had a consistent lowering effect on age at onset of FAD, but this was attenuated in SAD. This suggests that among individuals with a family history of AD and the APOE epsilon4 allele, additional genetic or environmental factors may accelerate the onset of dementia.

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  • Authors+Show Affiliations

    ,

    Gertrude H. Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.

    , , , , , , ,

    Source

    Archives of neurology 63:11 2006 Nov pg 1586-90

    MeSH

    Age of Onset
    Aged
    Aged, 80 and over
    Alzheimer Disease
    Apolipoprotein E4
    Caribbean Region
    Chi-Square Distribution
    Female
    Gene Frequency
    Genotype
    Hispanic Americans
    Humans
    Male
    Prospective Studies
    Risk Factors

    Pub Type(s)

    Comparative Study
    Journal Article
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17101827

    Citation

    Olarte, Lucia, et al. "Apolipoprotein E Epsilon4 and Age at Onset of Sporadic and Familial Alzheimer Disease in Caribbean Hispanics." Archives of Neurology, vol. 63, no. 11, 2006, pp. 1586-90.
    Olarte L, Schupf N, Lee JH, et al. Apolipoprotein E epsilon4 and age at onset of sporadic and familial Alzheimer disease in Caribbean Hispanics. Arch Neurol. 2006;63(11):1586-90.
    Olarte, L., Schupf, N., Lee, J. H., Tang, M. X., Santana, V., Williamson, J., ... Mayeux, R. (2006). Apolipoprotein E epsilon4 and age at onset of sporadic and familial Alzheimer disease in Caribbean Hispanics. Archives of Neurology, 63(11), pp. 1586-90.
    Olarte L, et al. Apolipoprotein E Epsilon4 and Age at Onset of Sporadic and Familial Alzheimer Disease in Caribbean Hispanics. Arch Neurol. 2006;63(11):1586-90. PubMed PMID: 17101827.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Apolipoprotein E epsilon4 and age at onset of sporadic and familial Alzheimer disease in Caribbean Hispanics. AU - Olarte,Lucia, AU - Schupf,Nicole, AU - Lee,Joseph H, AU - Tang,Ming-Xin, AU - Santana,Vincent, AU - Williamson,Jennifer, AU - Maramreddy,Prashanthi, AU - Tycko,Benjamin, AU - Mayeux,Richard, PY - 2006/11/15/pubmed PY - 2006/12/13/medline PY - 2006/11/15/entrez SP - 1586 EP - 90 JF - Archives of neurology JO - Arch. Neurol. VL - 63 IS - 11 N2 - BACKGROUND: The primary effect of the apolipoprotein E epsilon4 (APOE epsilon4) allele is on the age at onset of Alzheimer disease (AD). OBJECTIVE: To investigate whether the presence of the APOE epsilon4 allele can account for the earlier age at onset of familial AD (FAD) compared with sporadic AD (SAD). DESIGN: Population-based, case series ascertained in a prospective study of aging and dementia in Medicare recipients aged 65 years or older. SETTING: Clinics in northern Manhattan and in the Dominican Republic and Puerto Rico. PARTICIPANTS: There were 680 Caribbean Hispanic subjects: 111 patients with FAD, with at least 1 family member with dementia; 163 patients with SAD; and 406 elderly persons without dementia or other illnesses. Main Outcome Measure Age at onset of dementia was examined in relation to frequency of APOE epsilon4. Sex, education, and medical risk factors for stroke, hypertension, diabetes, and heart disease were examined as effect modifiers. RESULTS: The mean age at onset of AD was significantly lower in FAD than in SAD, and a statistically significant dose effect of the APOE epsilon4 allele was present for age at onset in FAD (P = .001) but not in SAD. The age at onset in patients homozygous for the APOE epsilon4 allele with FAD and SAD was similar. Compared with SAD, the major difference was younger age at onset in patients with FAD who were heterozygous for the APOE epsilon4 allele and those without an APOE epsilon4 allele. CONCLUSIONS: Apolipoprotein E epsilon4 had a consistent lowering effect on age at onset of FAD, but this was attenuated in SAD. This suggests that among individuals with a family history of AD and the APOE epsilon4 allele, additional genetic or environmental factors may accelerate the onset of dementia. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/17101827/Apolipoprotein_E_epsilon4_and_age_at_onset_of_sporadic_and_familial_Alzheimer_disease_in_Caribbean_Hispanics_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneur.63.11.1586 DB - PRIME DP - Unbound Medicine ER -