NeuroMolecular Medicine

, Volume 5, Issue 2, pp 133–146 | Cite as

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

  • 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 Hollingworth
  • Nicola 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
Original Article

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.

Index Entries

CTNNA3 α-T-catenin Alzheimer’s disease chromosome 10 amyloid Aβ age of onset APOE Wn 

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Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  • Victoria Busby
    • 1
  • Steven Goossens
    • 2
  • Petra Nowotny
    • 3
  • Gillian Hamilton
    • 1
  • Scott Smemo
    • 3
  • Denise Harold
    • 4
  • Dragana Turic
    • 4
  • Luke Jehu
    • 4
  • Amanda Myers
    • 5
  • Meredith Womick
    • 5
  • Daniel Woo
    • 5
  • Danielle Compton
    • 5
  • Lisa M. Doil
    • 10
  • Kristina M. Tacey
    • 10
  • Kit F. Lau
    • 10
  • Safa Al-Saraj
    • 1
  • Richard Killick
    • 1
  • Stuart Pickering-Brown
    • 1
  • Pamela Moore
    • 4
  • Paul Hollingworth
    • 4
  • Nicola Archer
    • 1
  • Catherine Foy
    • 1
  • Sarah Walter
    • 1
  • Corrine Lendon
    • 6
  • Takeshi Iwatsubo
    • 7
  • John C. Morris
    • 3
  • Joanne Norton
    • 3
  • David Mann
    • 8
  • Barbara Janssens
    • 2
  • John Hardy
    • 5
  • Michael O’Donovan
    • 4
  • Lesley Jones
    • 4
  • Julie Williams
    • 4
  • Peter Holmans
    • 9
  • Michael J. Owen
    • 4
  • Andrew Grupe
    • 10
  • John Powell
    • 1
  • Jolanda van Hengel
    • 2
  • Alison Goate
    • 3
  • Frans Van Roy
    • 2
  • Simon Lovestone
    • 1
  1. 1.Department of NeuroscienceInstitute of PsychiatryLondonUnited Kingdom
  2. 2.Molecular Cell Biology Unit, Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology (VIB)Ghent UniversityGhentBelgium
  3. 3.Departments of Psychiatry, Neurology and GeneticsWashington University School of MedicineSt. Louis
  4. 4.Department of Psychological MedicineUniversity of Wales College of MedicineCardiffUnited Kingdom
  5. 5.Laboratory of Neurogenetics, National Institute on AgingNational Institutes of HealthBethesda
  6. 6.Department of Psychiatry, University of BirminghamQueen Elizabeth Psychiatric HospitalBirminghamUnited Kingdom
  7. 7.Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical SciencesUniversity of TokyoTokyoJapan
  8. 8.Greater Manchester Neurosciences CentreHope HospitalUK
  9. 9.MRC Biostatistics UnitInstitute of Public HealthCambridgeUnited Kingdom
  10. 10.Celera DiagnosticsAlameda

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