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Heritability of plasma amyloid beta in typical late-onset Alzheimer's disease pedigrees.
Genet Epidemiol. 2001 Jul; 21(1):19-30.GE

Abstract

Plasma amyloid beta42 peptide (Abeta42) levels are significantly elevated in all genetic forms of early-onset Alzheimer's disease caused by familial Alzheimer's disease mutations or Down's syndrome. Moreover, recent studies have determined that both plasma Abeta42 and Abeta40 levels are significantly elevated in late-onset Alzheimer's disease (LOAD) patients, their cognitively normal first-degree relatives, and members of typical LOAD families when compared to appropriate controls. To determine the magnitude of the genetic component affecting plasma Abeta levels, we estimated the heritability of plasma Abeta42 and Abeta40 in 15 extended, multigenerational LOAD pedigrees, using a variance components method. Heritability estimates as high as 73 and 54% were found for plasma Abeta42 and Abeta40 levels, respectively. Inclusion of the ApoE epsilon4 dosage as a covariate was not found to have a significant effect on the heritability of these traits. These results suggest that genetic determinants other than ApoE account for a very substantial percentage of the phenotypic variance in plasma Abeta levels. The high heritability and the significant elevation of these traits in LOAD pedigrees suggest that at least some of the genetic determinants of plasma Abeta levels may lead to elevated Abeta and LOAD in these families. Thus, we suggest that plasma Abeta levels are quantitative traits that may be excellent surrogate markers for use in linkage analysis to identify loci that are important in typical LOAD.

Authors+Show Affiliations

Mayo Clinic Jacksonville, Jacksonville, Florida, 32224, USA.No 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
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11443731

Citation

Ertekin-Taner, N, et al. "Heritability of Plasma Amyloid Beta in Typical Late-onset Alzheimer's Disease Pedigrees." Genetic Epidemiology, vol. 21, no. 1, 2001, pp. 19-30.
Ertekin-Taner N, Graff-Radford N, Younkin LH, et al. Heritability of plasma amyloid beta in typical late-onset Alzheimer's disease pedigrees. Genet Epidemiol. 2001;21(1):19-30.
Ertekin-Taner, N., Graff-Radford, N., Younkin, L. H., Eckman, C., Adamson, J., Schaid, D. J., Blangero, J., Hutton, M., & Younkin, S. G. (2001). Heritability of plasma amyloid beta in typical late-onset Alzheimer's disease pedigrees. Genetic Epidemiology, 21(1), 19-30.
Ertekin-Taner N, et al. Heritability of Plasma Amyloid Beta in Typical Late-onset Alzheimer's Disease Pedigrees. Genet Epidemiol. 2001;21(1):19-30. PubMed PMID: 11443731.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Heritability of plasma amyloid beta in typical late-onset Alzheimer's disease pedigrees. AU - Ertekin-Taner,N, AU - Graff-Radford,N, AU - Younkin,L H, AU - Eckman,C, AU - Adamson,J, AU - Schaid,D J, AU - Blangero,J, AU - Hutton,M, AU - Younkin,S G, PY - 2001/7/10/pubmed PY - 2001/8/10/medline PY - 2001/7/10/entrez SP - 19 EP - 30 JF - Genetic epidemiology JO - Genet Epidemiol VL - 21 IS - 1 N2 - Plasma amyloid beta42 peptide (Abeta42) levels are significantly elevated in all genetic forms of early-onset Alzheimer's disease caused by familial Alzheimer's disease mutations or Down's syndrome. Moreover, recent studies have determined that both plasma Abeta42 and Abeta40 levels are significantly elevated in late-onset Alzheimer's disease (LOAD) patients, their cognitively normal first-degree relatives, and members of typical LOAD families when compared to appropriate controls. To determine the magnitude of the genetic component affecting plasma Abeta levels, we estimated the heritability of plasma Abeta42 and Abeta40 in 15 extended, multigenerational LOAD pedigrees, using a variance components method. Heritability estimates as high as 73 and 54% were found for plasma Abeta42 and Abeta40 levels, respectively. Inclusion of the ApoE epsilon4 dosage as a covariate was not found to have a significant effect on the heritability of these traits. These results suggest that genetic determinants other than ApoE account for a very substantial percentage of the phenotypic variance in plasma Abeta levels. The high heritability and the significant elevation of these traits in LOAD pedigrees suggest that at least some of the genetic determinants of plasma Abeta levels may lead to elevated Abeta and LOAD in these families. Thus, we suggest that plasma Abeta levels are quantitative traits that may be excellent surrogate markers for use in linkage analysis to identify loci that are important in typical LOAD. SN - 0741-0395 UR - https://www.unboundmedicine.com/medline/citation/11443731/Heritability_of_plasma_amyloid_beta_in_typical_late_onset_Alzheimer's_disease_pedigrees_ L2 - https://doi.org/10.1002/gepi.1015 DB - PRIME DP - Unbound Medicine ER -