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Apolipoprotein E epsilon4 allele and familial aggregation of Alzheimer disease.
Arch Neurol 1998; 55(6):810-6AN

Abstract

OBJECTIVE

To investigate the relationship among risk for Alzheimer disease (AD), familial aggregation of AD, and the apolipoprotein E (apoE) epsilon4 allele in first-degree relatives of probands with AD and known apoE genotype.

PATIENTS

Two hundred ninety subjects fulfilling the criteria of the National Institute of Neurological Communicative Disease and Stroke-Alzheimer's Disease and Related Disorders Association for probable AD were ascertained from March 1, 1992, to December 31, 1996, through consecutive admissions in several university hospitals.

DESIGN AND METHODS

Family data were collected on 1176 first-degree relatives (parents and siblings), aged 40 to 90 years. Most living relatives underwent a clinical examination, whereas we relied on family history for clinical data for deceased or unavailable relatives. First, we conducted standard survival analyses to estimate cumulative lifetime risk (LTR) for AD among relatives and to investigate for sex and apoE genotype effects on LTR. Then, we assessed to what extent clustering of secondary AD could be explained by the apoE epsilon4 allele by deriving the expected proportions of relatives with 0, 1, or 2 apoE epsilon4 alleles conditionally on the proband's genotype.

RESULTS

Cumulative LTR for AD among first-degree relatives increased significantly with the number of epsilon4 alleles present in the proband. By 90 years of age, LTRs in relatives of probands with epsilon3/epsilon3, epsilon3/epsilon4, and epsilon4/epsilon4 genotypes were 29.2%, 46.1%, and 61.4%, respectively. Significant sex-by-apoE genotype interaction effects on LTR were observed. Women had about a 2-fold higher risk for AD than men among relatives of epsilon4 carriers but not among relatives of non-epsilon4 carriers. The predicted proportion of epsilon4 carriers in relatives of probands with epsilon3/epsilon3 genotype remains about 50% lower than the corresponding LTR for AD, indicating that familial clustering of AD is largely due to other factors than the apoE epsilon4 allele. Although aggregation of AD in families of probands with the epsilon4 allele is more prominent, we estimated that AD would not develop in about 30% of female and up to 60% of male relatives carrying at least 1 epsilon4 allele, even by 90 years of age.

CONCLUSION

Our results support the hypothesis that the apoE epsilon4 allele enhances AD susceptibility, but putative factors enhancing risk for AD remain to be found.

Authors+Show Affiliations

Hôpital Saint-Louis, Institut National de la Santé et de la Recherche Médicale, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9626772

Citation

Martinez, M, et al. "Apolipoprotein E Epsilon4 Allele and Familial Aggregation of Alzheimer Disease." Archives of Neurology, vol. 55, no. 6, 1998, pp. 810-6.
Martinez M, Campion D, Brice A, et al. Apolipoprotein E epsilon4 allele and familial aggregation of Alzheimer disease. Arch Neurol. 1998;55(6):810-6.
Martinez, M., Campion, D., Brice, A., Hannequin, D., Dubois, B., Didierjean, O., ... Clerget-Darpoux, F. (1998). Apolipoprotein E epsilon4 allele and familial aggregation of Alzheimer disease. Archives of Neurology, 55(6), pp. 810-6.
Martinez M, et al. Apolipoprotein E Epsilon4 Allele and Familial Aggregation of Alzheimer Disease. Arch Neurol. 1998;55(6):810-6. PubMed PMID: 9626772.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apolipoprotein E epsilon4 allele and familial aggregation of Alzheimer disease. AU - Martinez,M, AU - Campion,D, AU - Brice,A, AU - Hannequin,D, AU - Dubois,B, AU - Didierjean,O, AU - Michon,A, AU - Thomas-Anterion,C, AU - Puel,M, AU - Frebourg,T, AU - Agid,Y, AU - Clerget-Darpoux,F, PY - 1998/6/17/pubmed PY - 1998/6/17/medline PY - 1998/6/17/entrez SP - 810 EP - 6 JF - Archives of neurology JO - Arch. Neurol. VL - 55 IS - 6 N2 - OBJECTIVE: To investigate the relationship among risk for Alzheimer disease (AD), familial aggregation of AD, and the apolipoprotein E (apoE) epsilon4 allele in first-degree relatives of probands with AD and known apoE genotype. PATIENTS: Two hundred ninety subjects fulfilling the criteria of the National Institute of Neurological Communicative Disease and Stroke-Alzheimer's Disease and Related Disorders Association for probable AD were ascertained from March 1, 1992, to December 31, 1996, through consecutive admissions in several university hospitals. DESIGN AND METHODS: Family data were collected on 1176 first-degree relatives (parents and siblings), aged 40 to 90 years. Most living relatives underwent a clinical examination, whereas we relied on family history for clinical data for deceased or unavailable relatives. First, we conducted standard survival analyses to estimate cumulative lifetime risk (LTR) for AD among relatives and to investigate for sex and apoE genotype effects on LTR. Then, we assessed to what extent clustering of secondary AD could be explained by the apoE epsilon4 allele by deriving the expected proportions of relatives with 0, 1, or 2 apoE epsilon4 alleles conditionally on the proband's genotype. RESULTS: Cumulative LTR for AD among first-degree relatives increased significantly with the number of epsilon4 alleles present in the proband. By 90 years of age, LTRs in relatives of probands with epsilon3/epsilon3, epsilon3/epsilon4, and epsilon4/epsilon4 genotypes were 29.2%, 46.1%, and 61.4%, respectively. Significant sex-by-apoE genotype interaction effects on LTR were observed. Women had about a 2-fold higher risk for AD than men among relatives of epsilon4 carriers but not among relatives of non-epsilon4 carriers. The predicted proportion of epsilon4 carriers in relatives of probands with epsilon3/epsilon3 genotype remains about 50% lower than the corresponding LTR for AD, indicating that familial clustering of AD is largely due to other factors than the apoE epsilon4 allele. Although aggregation of AD in families of probands with the epsilon4 allele is more prominent, we estimated that AD would not develop in about 30% of female and up to 60% of male relatives carrying at least 1 epsilon4 allele, even by 90 years of age. CONCLUSION: Our results support the hypothesis that the apoE epsilon4 allele enhances AD susceptibility, but putative factors enhancing risk for AD remain to be found. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/9626772/Apolipoprotein_E_epsilon4_allele_and_familial_aggregation_of_Alzheimer_disease_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/vol/55/pg/810 DB - PRIME DP - Unbound Medicine ER -