Skip Navigation


Human Molecular Genetics Advance Access originally published online on September 10, 2009
Human Molecular Genetics 2009 18(23):4492-4500; doi:10.1093/hmg/ddp408
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
18/23/4492    most recent
ddp408v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Mitchell, J. C.
Right arrow Articles by McLoughlin, D. M.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mitchell, J. C.
Right arrow Articles by McLoughlin, D. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

X11β rescues memory and long-term potentiation deficits in Alzheimer's disease APPswe Tg2576 mice

Jacqueline C. Mitchell1, Belall B. Ariff1, Darran M. Yates1, Kwok-Fai Lau1,2, Michael S. Perkinton1, Boris Rogelj1, John D. Stephenson1, Christopher C.J. Miller1,*,{dagger} and Declan M. McLoughlin1,3,{dagger}

1 MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, London SE5 8AF, UK, 2 Department of Biochemistry (Science), The Chinese University of Hong Kong, Shatin NT, Hong Kong SAR, The People's Republic of China and 3 Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, St Patrick's Hospital, Dublin 8, Ireland

* To whom correspondence should be addressed at: MRC Centre for Neurodegeneration Research, Department of Neuroscience P037, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK. Tel: +44 2078480393; Fax: +44 2077080017; Email: chris.miller{at}kcl.ac.uk

Received June 4, 2009; Accepted August 20, 2009

Increased production and deposition of amyloid β-protein (Aβ) are believed to be key pathogenic events in Alzheimer's disease. As such, routes for lowering cerebral Aβ levels represent potential therapeutic targets for Alzheimer's disease. X11β is a neuronal adaptor protein that binds to the intracellular domain of the amyloid precursor protein (APP). Overexpression of X11β inhibits Aβ production in a number of experimental systems. However, whether these changes to APP processing and Aβ production induced by X11β overexpression also induce beneficial effects to memory and synaptic plasticity are not known. We report here that X11β-mediated reduction in cerebral Aβ is associated with normalization of both cognition and in vivo long-term potentiation in aged APPswe Tg2576 transgenic mice that model the amyloid pathology of Alzheimer's disease. Overexpression of X11β itself has no detectable adverse effects upon mouse behaviour. These findings support the notion that modulation of X11β function represents a therapeutic target for Aβ-mediated neuronal dysfunction in Alzheimer's disease.

{dagger} These authors contributed equally.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.