Neurobiology of Disease (Mar 2007)
The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts
- Amanda J. Myers,
- Alan M. Pittman,
- Alice S. Zhao,
- Kristen Rohrer,
- Mona Kaleem,
- Lauren Marlowe,
- Andrew Lees,
- Doris Leung,
- Ian G. McKeith,
- Robert H. Perry,
- Chris M. Morris,
- John Q. Trojanowski,
- Christopher Clark,
- Jason Karlawish,
- Steve Arnold,
- Mark S. Forman,
- Vivianna Van Deerlin,
- Rohan de Silva,
- John Hardy
Affiliations
- Amanda J. Myers
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3707, USA
- Alan M. Pittman
- Reta Lila Weston Institute of Neurological Studies, University College London, 1 Wakefield Street, London WC1N 1PJ, UK; Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London WC1N 3BG, UK
- Alice S. Zhao
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3707, USA
- Kristen Rohrer
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3707, USA
- Mona Kaleem
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3707, USA
- Lauren Marlowe
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3707, USA
- Andrew Lees
- Reta Lila Weston Institute of Neurological Studies, University College London, 1 Wakefield Street, London WC1N 1PJ, UK; Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London WC1N 3BG, UK; Sara Koe PSP Research Centre, Institute of Neurology, 1 Wakefield Street, London WC1N 1PJ, UK
- Doris Leung
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3707, USA
- Ian G. McKeith
- Institute for Ageing and Health, University of Newcastle, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, NE4 6BE, UK
- Robert H. Perry
- Institute for Ageing and Health, University of Newcastle, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, NE4 6BE, UK
- Chris M. Morris
- Institute for Ageing and Health, University of Newcastle, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, NE4 6BE, UK
- John Q. Trojanowski
- Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
- Christopher Clark
- Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
- Jason Karlawish
- Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
- Steve Arnold
- Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
- Mark S. Forman
- Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
- Vivianna Van Deerlin
- Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
- Rohan de Silva
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3707, USA; Reta Lila Weston Institute of Neurological Studies, University College London, 1 Wakefield Street, London WC1N 1PJ, UK
- John Hardy
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3707, USA; Reta Lila Weston Institute of Neurological Studies, University College London, 1 Wakefield Street, London WC1N 1PJ, UK; Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London WC1N 3BG, UK; Corresponding author. Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, 35 Convent Drive, Bethesda, MD20892, USA. Fax: +1 301 451 7295.
- Journal volume & issue
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Vol. 25,
no. 3
pp. 561 – 570
Abstract
Previously we have shown that the H1c haplotype on the background of the H1 clade of haplotypes at the MAPT locus is associated with increased risk for progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Alzheimer’s disease (AD). Here we replicated the association with AD in an additional autopsy confirmed series. We show that this haplotype increases both the expression of total MAPT transcript as well as specifically increasing the proportion of 4 microtubule binding repeat containing transcripts. We discuss these findings both in terms of the problems facing the dissection of the etiologies of complex traits and the pathogenesis of the tauopathies.
