Alpha-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

Victoria Busby, Steven Goossens, Petra Nowotny, Gillian Hamilton, Scott Smemo, Denise Harold, Dragana Turic, Luke Jehu, Amanda Myers, Meredith Womick, Daniel Woo, Danielle Compton, Lisa M. Doil, Kristina M. Tacey, Kit F. Lau, Safa Al-Saraj, Richard Killick, Stuart Pickering-Brown, Pamela Moore, Paul HollingworthNicola Archer, Catherine Foy, Sarah Walter, Corrine Lendon, Takeshi Iwatsubo, John C. Morris, Joanne Norton, David Mann, Barbara Janssens, John Hardy, Michael O'Donovan, Lesley Jones, Julie Williams, Peter Holmans, Michael J. Owen, Andrew Grupe, John Powell, Jolanda van Hengel, Alison Goate, Frans Van Roy, Simon Lovestone

Research output: Contribution to journalArticle

Abstract

The gene encoding alpha-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 alpha-T-catenin is expressed in human brain, and like other alpha-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 Abeta 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.
Original languageEnglish
Pages (from-to)133-146
Number of pages14
JournalNeuromolecular Medicine
Volume5
Issue number2
DOIs
Publication statusPublished - Apr 2004

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Keywords

  • CTNNA3
  • a-T-catenin
  • Alzheimer's disease
  • chromosome 10
  • age of consent
  • APOE
  • Wn

Cite this

Busby, V., Goossens, S., Nowotny, P., Hamilton, G., Smemo, S., Harold, D., Turic, D., Jehu, L., Myers, A., Womick, M., Woo, D., Compton, D., Doil, L. M., Tacey, K. M., Lau, K. F., Al-Saraj, S., Killick, R., Pickering-Brown, S., Moore, P., ... Lovestone, S. (2004). Alpha-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. Neuromolecular Medicine, 5(2), 133-146. https://doi.org/10.1385/nmm:5:2:133