Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease.

Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease. Research Abstract Details 

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Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease. Abstract Text:

Giancarlo V De Ferrari,Andreas Papassotiropoulos,Travis Biechele,Fabienne Wavrant De-Vrieze,Miguel E Avila,Michael B Major,Amanda Myers,Katia ,Juan P ,Alice Zhao,M Axel Wollmer,Roger M Nitsch,Christoph Hock,Chris M Morris,John Hardy,Randall T Moon,

Genome-wide linkage studies have defined a broad susceptibility region for late-onset Alzheimer's disease on chromosome 12, which contains the Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) gene, a coreceptor for Wnt signaling. Here, we report the association between common LRP6 variants and late-onset Alzheimer's disease in a multicenter case-control series as well as in a large family-based series ascertained by the National Institute of Mental Health-National Institute on Aging Genetics Initiative. As shown in the genome-wide linkage studies, our association depends mainly on apolipoprotein E-epsilon4 (APOE-epsilon4) carrier status. Haplotype tagging single-nucleotide polymorphisms (SNPs) with a set of seven allelic variants of LRP6 identified a putative risk haplotype, which includes a highly conserved coding sequence SNP: Ile-1062 --> Val. Functional analyses revealed that the associated allele Val-1062, an allele previously linked to low bone mass, has decreased beta-catenin signaling in HEK293T cells. Our study unveils a genetic relationship between LRP6 and APOE and supports the hypothesis that altered Wnt/beta-catenin signaling may be involved in this neurodegenerative disease.

Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease. Publishing Authors By Initials

GV De Ferrari,A Papassotiropoulos,T Biechele,F Wavrant De-Vrieze,ME Avila,MB Major,A Myers,K ,JP ,A Zhao,MA Wollmer,RM Nitsch,C Hock,CM Morris,J Hardy,RT Moon,

For similar proteins: armadillo domain proteins: beta catenin research abstracts see: proteins: armadillo domain proteins: beta catenin research

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Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 9434-9

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 21

MONTH: 05

YEAR: 2007

Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease. Keywords Mesh Terms:

KEYWORDS: beta Catenin

MESH TERMS: metabolism

Chemical & Substance for Abstract: Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease. Information

Substance Name: Valine

Registry Number: 7004-03-7

Grant and Affiliation Information for Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease.

AFFILIATION: Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, WA 98195, USA. gdeferrari@udec.cl

Country: United States

AGENCY: United States NIMH

GRANT: U01 MH 46372

ACRONYM: MH

MEDLINETA: Proc Natl Acad Sci U S A

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