@article{83ec53a60fe442caa9e4d8e2a6b25aed,
title = "α-T-Catenin Is Expressed in Human Brain and Interacts with the Wnt Signaling Pathway but Is Not Responsible for Linkage to Chromosome 10 in Alzheimer's Disease",
abstract = "The gene encoding α-T-catenin, CTNNA3, is positioned within a region on chromosome 10, showing strong evidence of linkage to Alzheimer's disease (AD), and is therefore a good positional candidate gene for this disorder. We have demonstrated that α-T-catenin is expressed in human brain, and like other α-catenins, it inhibits Wnt signaling and is therefore also a functional candidate. We initially genotyped two single-nucleotide polymorphisms (SNPs) in the gene, in four independent samples comprising over 1200 cases and controls but failed to detect an association with either SNP. Similarly, we found no evidence for association between CTNNA3 and AD in a sample of subjects showing linkage to chromosome 10, nor were these SNPs associated with Aβ deposition in brain. To comprehensively screen the gene, we genotyped 30 additional SNPs in a subset of the cases and controls (n > 700). None of these SNPs was associated with disease. Although an excellent candidate, we conclude that CTNNA3 is unlikely to account for the AD susceptibility locus on chromosome 10.",
keywords = "APOE, Age of onset, Alzheimer's disease, Amyloid, Aβ, CTNNA3, Chromosome 10, Wn, α-T-catenin",
author = "Victoria Busby and Steven Goossens and Petra Nowotny and Gillian Hamilton and Scott Smemo and Denise Harold and Dragana Turic and Luke Jehu and Amanda Myers and Meredith Womick and Daniel Woo and Danielle Compton and Doil, {Lisa M.} and Tacey, {Kristina M.} and Lau, {Kit F.} and Safa Al-Saraj and Richard Killick and Stuart Pickering-Brown and Pamela Moore and Paul Hollingworth and Nicola Archer and Catherine Foy and Sarah Walter and Corrine Lendon and Takeshi Iwatsubo and Morris, {John C.} and Joanne Norton and David Mann and Barbara Janssens and John Hardy and Michael O'Donovan and Lesley Jones and Julie Williams and Peter Holmans and Owen, {Michael J.} and Andrew Grupe and John Powell and {Van Hengel}, Jolanda and Alison Goate and {Van Roy}, Frans and Simon Lovestone",
note = "Funding Information: None of this work would be possible without the generous participation of the patients and their families. AG is supported by NIH grant AG16208 and AMG and JCM are supported by NIH grant AG5681. JH was supported by AG16208 and is now part of the NIA intramural program. JH also thanks the Verum Foundation. The Mayo sample collection is supported by NIA grants AG 06786 and AG 16574. The Cardiff and IOP groups were supported the Medical Research Council (UK), the Alzheimer{\textquoteright}s Research Trust, and Research into Ageing. FvR is funded by grants from the GOA (Geconcerteerde Onderzoeksacties), Ghent University, and from the FWO-Vlaanderen (Fund for Scientific Research, Flanders). SG and JvH received fellowships from the GOA and the FWO, respectively.",
year = "2004",
doi = "10.1385/NMM:5:2:133",
language = "English",
volume = "5",
pages = "133--146",
journal = "NeuroMolecular Medicine",
issn = "1535-1084",
number = "2",
}