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

Jason J Corneveaux; Winnie S Liang; Eric M Reiman; Jennifer A Webster; Amanda J Myers; Victoria L Zismann; Keta D Joshipura; John V Pearson; Diane Hu-Lince; David W Craig; Keith D Coon; Travis Dunckley; Daniel Bandy; Wendy Lee; Kewei Chen; Thomas G Beach; Diego Mastroeni; Andrew Grover; Rivka Ravid; Sigrid B Sando; Jan O Aasly; Reinhard Heun; Frank Jessen; Heike Kölsch; Joseph Rogers; Michael L Hutton; Stacey Melquist; Ron C Petersen; Gene E Alexander; Richard J Caselli; Andreas Papassotiropoulos; Dietrich A Stephan; Matthew J Huentelman

doi:10.1016/j.neurobiolaging.2008.07.014

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

Journal article

Open access

Peer reviewed

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

Jason J Corneveaux, Winnie S Liang, Eric M Reiman, Jennifer A Webster, Amanda J Myers, Victoria L Zismann, Keta D Joshipura, John V Pearson, Diane Hu-Lince, David W Craig, …

Neurobiology of aging, Vol.31(6), pp.901-909

2010-06

DOI: https://doi.org/10.1016/j.neurobiolaging.2008.07.014

PMCID: PMC2913703

PMID: 18789830

Abstract

Genetics

Expression profiling

Imaging

Memory

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.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.108 Molecular & Cell Biology - Cancer & Development; 1.108.2215 Hippo Pathway
Web Of Science research areas: Geriatrics & Gerontology; Neurosciences
ESI research areas: Neuroscience & Behavior

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Title: Evidence for an association between KIBRA and late-onset Alzheimer's disease
Creators: Jason J Corneveaux - Translational Genomics Research Institute (TGen), Neurogenomics Division, 445 N. Fifth Street, Phoenix, AZ 85004, USA
Winnie S Liang - Translational Genomics Research Institute (TGen), Neurogenomics Division, 445 N. Fifth Street, Phoenix, AZ 85004, USA
Eric M Reiman - Translational Genomics Research Institute (TGen), Neurogenomics Division, 445 N. Fifth Street, Phoenix, AZ 85004, USA
Jennifer A Webster - Translational Genomics Research Institute (TGen), Neurogenomics Division, 445 N. Fifth Street, Phoenix, AZ 85004, USA
Amanda J Myers - University of Miami, Miller School of Medicine, Department of Psychiatry and Behavioral Sciences, 1695 N.W. 9th Avenue, PO Box 016960 (D-29), Miami, FL 33101, USA
Victoria L Zismann - Translational Genomics Research Institute (TGen), Neurogenomics Division, 445 N. Fifth Street, Phoenix, AZ 85004, USA
Keta D Joshipura - Translational Genomics Research Institute (TGen), Neurogenomics Division, 445 N. Fifth Street, Phoenix, AZ 85004, USA
John V Pearson - Translational Genomics Research Institute (TGen), Neurogenomics Division, 445 N. Fifth Street, Phoenix, AZ 85004, USA
Diane Hu-Lince - Translational Genomics Research Institute (TGen), Neurogenomics Division, 445 N. Fifth Street, Phoenix, AZ 85004, USA
David W Craig - Translational Genomics Research Institute (TGen), Neurogenomics Division, 445 N. Fifth Street, Phoenix, AZ 85004, USA
Keith D Coon - Translational Genomics Research Institute (TGen), Neurogenomics Division, 445 N. Fifth Street, Phoenix, AZ 85004, USA
Travis Dunckley - Translational Genomics Research Institute (TGen), Neurogenomics Division, 445 N. Fifth Street, Phoenix, AZ 85004, USA
Daniel Bandy - Arizona Alzheimer's Consortium, 901 E. Willetta Street, Phoenix, AZ 85006, USA
Wendy Lee - Arizona Alzheimer's Consortium, 901 E. Willetta Street, Phoenix, AZ 85006, USA
Kewei Chen - Arizona Alzheimer's Consortium, 901 E. Willetta Street, Phoenix, AZ 85006, USA
Thomas G Beach - Arizona Alzheimer's Consortium, 901 E. Willetta Street, Phoenix, AZ 85006, USA
Diego Mastroeni - Arizona Alzheimer's Consortium, 901 E. Willetta Street, Phoenix, AZ 85006, USA
Andrew Grover - Arizona Alzheimer's Consortium, 901 E. Willetta Street, Phoenix, AZ 85006, USA
Rivka Ravid - Dutch Royal Academy of Arts and Sciences, Netherlands Institute for Neurosciences, Meibergdreef 47 AB, Amsterdam, The Netherlands
Sigrid B Sando - Department of Neurology, St. Olav's Hospital, Edvard Griegs Gate 8, 7006 Trondheim, Norway
Jan O Aasly - Department of Neurology, St. Olav's Hospital, Edvard Griegs Gate 8, 7006 Trondheim, Norway
Reinhard Heun - Department of Psychiatry, University of Bonn, Bonn, Germany
Frank Jessen - Department of Psychiatry, University of Bonn, Bonn, Germany
Heike Kölsch - Department of Psychiatry, University of Bonn, Bonn, Germany
Joseph Rogers - Arizona Alzheimer's Consortium, 901 E. Willetta Street, Phoenix, AZ 85006, USA
Michael L Hutton - Mayo Clinic, Department of Neuroscience, 4500 San Pablo Road, Jacksonville, FL 32224, USA
Stacey Melquist - Mayo Clinic, Department of Neuroscience, 4500 San Pablo Road, Jacksonville, FL 32224, USA
Ron C Petersen - Mayo Clinic, Department of Neurology, 200 First Street S.W., Rochester, MN 55905, USA
Gene E Alexander - Arizona Alzheimer's Consortium, 901 E. Willetta Street, Phoenix, AZ 85006, USA
Richard J Caselli - Arizona Alzheimer's Consortium, 901 E. Willetta Street, Phoenix, AZ 85006, USA
Andreas Papassotiropoulos - Translational Genomics Research Institute (TGen), Neurogenomics Division, 445 N. Fifth Street, Phoenix, AZ 85004, USA
Dietrich A Stephan - Translational Genomics Research Institute (TGen), Neurogenomics Division, 445 N. Fifth Street, Phoenix, AZ 85004, USA
Matthew J Huentelman - Translational Genomics Research Institute (TGen), Neurogenomics Division, 445 N. Fifth Street, Phoenix, AZ 85004, USA
Publication Details: Neurobiology of aging, Vol.31(6), pp.901-909
Publisher: Elsevier Inc
Academic Unit: Miller School of Medicine; Cell Biology Research
Language: English
Resource Type: Journal article
PMID: 18789830
PMCID: PMC2913703
Record Identifier: 991031559569302976