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Human Molecular Genetics Advance Access published online on July 6, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi241
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© The Author 2005. Published by Oxford University Press. All rights reserved
Received April 21, 2005
Revised June 8, 2005
Accepted June 29, 2005

Article

The H1c Haplotype at the MAPT Locus is associated with Alzheimer's Disease

Amanda J. Myers 1, Mona Kaleem 1, Lauren Marlowe 1, Alan M. Pittman 2, Andrew Lees 3, Hon Chung Fung 4, Jaime Duckworth 1, Doris Leung 1, Alison Gibson 5, Chris M. Morris 5, Rohan de Silva 2, and John Hardy 6*

1 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda MD 20892-3707, USA.
2 Reta Lila Weston Institute of Neurological Studies, University College London, Windeyer Building, 46 Cleveland Street, London, W1T 4JF, UK.; Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
3 Reta Lila Weston Institute of Neurological Studies, University College London, Windeyer Building, 46 Cleveland Street, London, W1T 4JF, 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
4 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, Windeyer Building, 46 Cleveland Street, London, W1T 4JF, UK.; Second Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, 199 Tung Hwa North Road, Taipei, Taiwan 10591
5 Institute for Ageing and Health, MRC Building, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, NE4 6BE, UK.
6 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Porter Neuroscience Building, 35 Convent Drive, Bethesda MD20892-3707, USA.; Reta Lila Weston Institute of Neurological Studies, University College London, Windeyer Building, 46 Cleveland Street, London, W1T 4JF, UK.; Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, WC1N 3BG, UK.

* To whom correspondence should be addressed.
John Hardy, E-mail: mailto:hardyj{at}mail.nih.gov


  Abstract

While it is clear that microtubule associated protein tau (MAPT) is involved in Alzheimer's disease (AD) pathology, it has not been clear whether it is involved genetically. We recently have examined the MAPT locus in progressive supranuclear palsy and found that a haplotype (H1c) on the background of the well-described H1 clade is associated with PSP. Here we report that the same haplotype is associated with the risk of Alzheimer's disease in two autopsy confirmed series of cases with ages at death >65 years.


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