TY - JOUR
T1 - Evidence for an association between KIBRA and late-onset Alzheimer's disease
AU - Corneveaux, Jason J.
AU - Liang, Winnie S.
AU - Reiman, Eric M.
AU - Webster, Jennifer A.
AU - Myers, Amanda J.
AU - Zismann, Victoria L.
AU - Joshipura, Keta D.
AU - Pearson, John V.
AU - Hu-Lince, Diane
AU - Craig, David W.
AU - Coon, Keith D.
AU - Dunckley, Travis
AU - Bandy, Daniel
AU - Lee, Wendy
AU - Chen, Kewei
AU - Beach, Thomas G.
AU - Mastroeni, Diego
AU - Grover, Andrew
AU - Ravid, Rivka
AU - Sando, Sigrid B.
AU - Aasly, Jan O.
AU - Heun, Reinhard
AU - Jessen, Frank
AU - Kölsch, Heike
AU - Rogers, Joseph
AU - Hutton, Michael L.
AU - Melquist, Stacey
AU - Petersen, Ron C.
AU - Alexander, Gene E.
AU - Caselli, Richard J.
AU - Papassotiropoulos, Andreas
AU - Stephan, Dietrich A.
AU - Huentelman, Matthew J.
N1 - Funding Information:
We would like to thank Christopher B. Heward of Kronos Life Sciences Laboratories for support on the first AD association study. This study was also funded by the National Institute on Aging (Arizona Alzheimer's Disease Center P30 AG19610, RO1 AG023193, Mayo Clinic Alzheimer's Disease Center P50 AG16574 and Intramural Research Program, P30 AG19610 to E.M.R.), the National Institute of Mental Health (RO1 MH57899 to E.M.R.), the Arizona Alzheimer's Consortium (Arizona Department of Health Services to E.M.R.), the Banner Alzheimer Foundation (to E.M.R.), the Mayo Clinic Foundation (to R.J.C.), the National Alzheimer's Coordinating Center (U01 AG016976), the National Institutes of Health (R01 NS059873 to M.J.H.) and the state of Arizona. We thank our research volunteers and their families for their generous participation and Drs. Creighton Phelps, Marcelle Morrison-Bogorad, Marilyn Miller, and Walter Kukull for their assistance in the acquisition of tissue samples and data, and directors, pathologists, and technologists from the following ADCs and brain banks: Lucia Sue (Sun Health Research Institute and Arizona Alzheimer's Disease Center); Ruth Seemann and Dan Brady (National Institute on Aging); Juan C. Troncoso and Olga Pletnikova (John Hopkins, P50 AG05146); Harry Vinters and Justine Pomakian (University of California, Los Angeles, P50 AG16570); Christine M. Hulette (The Kathleen Price Bryan Brain Bank, Duke University Medical Center, P50 AG05128, RO1 NS39764, RO1 MH60451, and GlaxoSmithKline); Dikran Horoupian, Ahmad Salehi (Stanford University, P30 AG17824); Jean Paul Vonsattel (New York Brain Bank, Taub Institute, Columbia University, P50 AG08702); E. Tessa Hedley-Whyte, Karlotta Fitch (Massachusetts General Hospital, P50 AG05134); Roger Albin, Lisa Bain, and Eszter Gombosi (University of Michigan, P50 AG08671); William Markesbery, Sonya Anderson (University of Kentucky, P50 AG05144); Dennis W. Dickson and Natalie Thomas (Mayo Clinic, Jacksonville, P50 AG16574 and P50 AG25711); Carol A. Miller, Jenny Tang, and Dimitri Diaz (University of Southern California, P50 AG05142); Dan McKeel, John C. Morris, Eugene Johnson, Jr., Virginia Buckles, and Deborah Carter (Washington University, St Louis, P50 AG 05681); Thomas Montine and Aimee Schantz (University of Washington, P50 AG05136); John Q. Trojanowski, Virginia M. Lee, Vivianna Van Deerlin, and Terry Schuck (University of Pennsylvania); Ann C. McKee and Carol Kubilus (Boston University, P30 AG13846); Bruce H. Wainer and Marla Gearing (Emory University, AG025688); Charles L. White, III, Roger Rosenberg, Marilyn Howell, and Joan Reisch (University of Texas, Southwestern Medical School, P30-AG12300); William Ellis and Mary Ann Jarvis, (University of California, Davis, P30 AG AG01542); David A. Bennett, Julie A. Schneider, Karen Skish, and Wayne T. Longman (Rush University Medical Center, P30 AG10161); Deborah C. Mash, Margaret J. Basile, and Mitsuko Tanaka University of Miami/NPF Brain Endowment Bank); and Nick Lehmans (Translational Genomics Research Institute). Additional support was provided by the Johnnie B. Byrd Sr. Alzheimer's Disease and Research Institute, the Swiss National Science Foundation (PP00B-68859), the Verum Foundation, the Bisgrove charitable donation, the NIH Neuroscience Blueprint (U24NS051872), the ENDGAME Consortium (UO1HL084744), a National Institute on Aging grant to Carl Cotman (University of California, Irvine, P50 AG23173) and the state of Arizona.
Funding Information:
Funding: NIH NINDS grant #NS059873A as well as funding from Science Foundation Arizona.
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
KW - Expression profiling
KW - Genetics
KW - Imaging
KW - Memory
UR - http://www.scopus.com/inward/record.url?scp=77951976812&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951976812&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2008.07.014
DO - 10.1016/j.neurobiolaging.2008.07.014
M3 - Article
C2 - 18789830
AN - SCOPUS:77951976812
SN - 0197-4580
VL - 31
SP - 901
EP - 909
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 6
ER -