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. SandoJan 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

Research output: Contribution to journalArticle

77 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)901-909
Number of pages9
JournalNeurobiology of Aging
Volume31
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • Expression profiling
  • Genetics
  • Imaging
  • Memory

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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  • Cite this

    Corneveaux, J. J., Liang, W. S., Reiman, E. M., Webster, J. A., Myers, A. J., Zismann, V. L., Joshipura, K. D., Pearson, J. V., Hu-Lince, D., Craig, D. W., Coon, K. D., Dunckley, T., Bandy, D., Lee, W., Chen, K., Beach, T. G., Mastroeni, D., Grover, A., Ravid, R., ... Huentelman, M. J. (2010). Evidence for an association between KIBRA and late-onset Alzheimer's disease. Neurobiology of Aging, 31(6), 901-909. https://doi.org/10.1016/j.neurobiolaging.2008.07.014