Tags

Type your tag names separated by a space and hit enter

Apolipoprotein E genotype in patients with Alzheimer's disease: implications for the risk of dementia among relatives.
Ann Neurol. 1995 Nov; 38(5):797-808.AN

Abstract

Numerous studies have shown that the risk of Alzheimer's disease (AD) is associated with the dose of the epsilon 4 allele of apolipoprotein E (ApoE). However, more than one third of AD patients lack epsilon 4 and many persons having epsilon 4 survive cognitively intact to old age. We evaluated the lifetime risk of disease in 3,999 first-degree relatives of 549 probands who met the criteria for probable or definite AD and whose ApoE genotypes were known. ApoE genotypes for relatives were not determined. After age 65 the risk among relatives was proportional, as much as 7 to 10% at age 85, to the number of epsilon 4 alleles present in the proband. Risks to relatives of ApoE 2/2 and 2/3 probands were nearly identical at all ages to risks for relatives of ApoE 3/3 probands. The expected proportion of relatives having at least one epsilon 4 allele was calculated for each genotype group based on the distribution of parents, sibs, and offspring in the sample. Among relatives in the ApoE 3/3 group, the lifetime risk for AD by age 90 was three times greater than the expected proportion of epsilon 4 carriers, suggesting that factors other than ApoE contribute to AD susceptibility. Furthermore, the 44% risk of AD by age 93 among relatives of ApoE 4/4 probands indicates that as many as 50% of people having at least one epsilon 4 allele do not develop AD. We also found that among male relatives, risk of AD in the ApoE 3/4 group was similar to that for the ApoE 3/3 group but significantly less than the risk for the ApoE 4/4 group. In contrast, among female relatives the risk for the ApoE 3/4 group was nearly twice that for the ApoE 3/3 group and identical to the risk for the ApoE 4/4 group. These findings are consistent with a sex-modification effect of the E4 isoform on disease susceptibility.

Links

Publisher Full Text

Authors+Show Affiliations

Farrer LA
Department of Neurology, Boston University School of Medicine, MA 02118, USA.
Cupples LA
No affiliation info available
van Duijn CM
No affiliation info available
Kurz A
No affiliation info available
Zimmer R
No affiliation info available
Müller U
No affiliation info available
Green RC
No affiliation info available
Clarke V
No affiliation info available
Shoffner J
No affiliation info available
Wallace DC
No affiliation info available

MeSH

Age of OnsetAgedAged, 80 and overAlzheimer DiseaseApolipoproteins ECohort StudiesFemaleGenotypeHumansMaleMiddle AgedPolymorphism, GeneticProportional Hazards ModelsRisk FactorsSensitivity and SpecificitySex Distribution

Pub Type(s)

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

Language

eng

PubMed ID

7486872

Citation

Farrer, L A., et al. "Apolipoprotein E Genotype in Patients With Alzheimer's Disease: Implications for the Risk of Dementia Among Relatives." Annals of Neurology, vol. 38, no. 5, 1995, pp. 797-808.
Farrer LA, Cupples LA, van Duijn CM, et al. Apolipoprotein E genotype in patients with Alzheimer's disease: implications for the risk of dementia among relatives. Ann Neurol. 1995;38(5):797-808.
Farrer, L. A., Cupples, L. A., van Duijn, C. M., Kurz, A., Zimmer, R., Müller, U., Green, R. C., Clarke, V., Shoffner, J., & Wallace, D. C. (1995). Apolipoprotein E genotype in patients with Alzheimer's disease: implications for the risk of dementia among relatives. Annals of Neurology, 38(5), 797-808.
Farrer LA, et al. Apolipoprotein E Genotype in Patients With Alzheimer's Disease: Implications for the Risk of Dementia Among Relatives. Ann Neurol. 1995;38(5):797-808. PubMed PMID: 7486872.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apolipoprotein E genotype in patients with Alzheimer's disease: implications for the risk of dementia among relatives. A1 - Farrer,L A, AU - Cupples,L A, AU - van Duijn,C M, AU - Kurz,A, AU - Zimmer,R, AU - Müller,U, AU - Green,R C, AU - Clarke,V, AU - Shoffner,J, AU - Wallace,D C, PY - 1995/11/1/pubmed PY - 1995/11/1/medline PY - 1995/11/1/entrez SP - 797 EP - 808 JF - Annals of neurology JO - Ann Neurol VL - 38 IS - 5 N2 - Numerous studies have shown that the risk of Alzheimer's disease (AD) is associated with the dose of the epsilon 4 allele of apolipoprotein E (ApoE). However, more than one third of AD patients lack epsilon 4 and many persons having epsilon 4 survive cognitively intact to old age. We evaluated the lifetime risk of disease in 3,999 first-degree relatives of 549 probands who met the criteria for probable or definite AD and whose ApoE genotypes were known. ApoE genotypes for relatives were not determined. After age 65 the risk among relatives was proportional, as much as 7 to 10% at age 85, to the number of epsilon 4 alleles present in the proband. Risks to relatives of ApoE 2/2 and 2/3 probands were nearly identical at all ages to risks for relatives of ApoE 3/3 probands. The expected proportion of relatives having at least one epsilon 4 allele was calculated for each genotype group based on the distribution of parents, sibs, and offspring in the sample. Among relatives in the ApoE 3/3 group, the lifetime risk for AD by age 90 was three times greater than the expected proportion of epsilon 4 carriers, suggesting that factors other than ApoE contribute to AD susceptibility. Furthermore, the 44% risk of AD by age 93 among relatives of ApoE 4/4 probands indicates that as many as 50% of people having at least one epsilon 4 allele do not develop AD. We also found that among male relatives, risk of AD in the ApoE 3/4 group was similar to that for the ApoE 3/3 group but significantly less than the risk for the ApoE 4/4 group. In contrast, among female relatives the risk for the ApoE 3/4 group was nearly twice that for the ApoE 3/3 group and identical to the risk for the ApoE 4/4 group. These findings are consistent with a sex-modification effect of the E4 isoform on disease susceptibility. SN - 0364-5134 UR - https://www.unboundmedicine.com/medline/citation/7486872/Apolipoprotein_E_genotype_in_patients_with_Alzheimer's_disease:_implications_for_the_risk_of_dementia_among_relatives_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0364-5134&date=1995&volume=38&issue=5&spage=797 DB - PRIME DP - Unbound Medicine ER -