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Evidence for an association between KIBRA and late-onset Alzheimer's disease

Corneveaux, Jason J. and Liang, Winnie S. and Reiman, Eric M. and Webster, Jennifer A. and Myers, Amanda J. and Zismann, Victoria L. and Joshipura, Keta D. and Pearson, John V. and Hu-Lince, Diane and Craig, David W. and Coon, Keith D. and Dunckley, Travis and Bandy, Daniel and Lee, Wendy and Chen, Kewei and Beach, Thomas G. and Mastroeni, Diego and Grover, Andrew and Ravid, Rivka and Sando, Sigrid B. and Aasly, Jan O. and Heun, Reinhard and Jessen, Frank and Kölsch, Heike and Rogers, Joseph and Hutton, Michael L. and Melquist, Stacey and Petersen, Ron C. and Alexander, Gene E. and Caselli, Richard J. and Papassotiropoulos, Andreas and Stephan, Dietrich A. and Huentelman, Matthew J.. (2008) Evidence for an association between KIBRA and late-onset Alzheimer's disease. Neurobiology of aging, Vol. 31, H. 6. pp. 901-909.

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Official URL: http://edoc.unibas.ch/dok/A5257143

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Abstract

We recently reported evidence for an association between the individual variation in normal human episodic memory and a common variant of the KIBRA gene, KIBRA rs17070145 (T-allele). Since memory impairment is a cardinal clinical feature of Alzheimer's disease (AD), we investigated the possibility of an association between the KIBRA gene and AD using data from neuronal gene expression, brain imaging studies, and genetic association tests. KIBRA was significantly over-expressed and three of its four known binding partners under-expressed in AD-affected hippocampal, posterior cingulate and temporal cortex regions (P>0.010, corrected) in a study of laser-capture microdissected neurons. Using positron emission tomography in a cohort of cognitively normal, late-middle-aged persons genotyped for KIBRA rs17070145, KIBRA T non-carriers exhibited lower glucose metabolism than did carriers in posterior cingulate and precuneus brain regions (P>0.001, uncorrected). Lastly, non-carriers of the KIBRA rs17070145 T-allele had increased risk of late-onset AD in an association study of 702 neuropathologically verified expired subjects (P=0.034; OR=1.29) and in a combined analysis of 1026 additional living and expired subjects (P=0.039; OR=1.26). Our findings suggest that KIBRA is associated with both individual variation in normal episodic memory and predisposition to AD.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Life Sciences Training Facility (Papassotiropoulos)
07 Faculty of Psychology > Departement Psychologie > Forschungsbereich Klinische Psychologie und Neurowissenschaften > Molecular Psychology (Papassotiropoulos)
UniBasel Contributors:Papassotiropoulos, Andreas
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier Science
ISSN:0197-4580
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:09
Deposited On:22 Mar 2012 13:30

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