title: Evidence for an association between KIBRA and late-onset Alzheimer's disease.
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.
authors.affiliation: Translational Genomics Research Institute (TGen), Neurogenomics Division, Phoenix, AZ 85004, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Corneveaux
authors.forename: Winnie S
authors.initials: WS
authors.lastname: Liang
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Webster
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Myers
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Zismann
authors.forename: Keta D
authors.initials: KD
authors.lastname: Joshipura
authors.forename: John V
authors.initials: JV
authors.lastname: Pearson
authors.forename: Diane
authors.initials: D
authors.lastname: Hu-Lince
authors.forename: David W
authors.initials: DW
authors.lastname: Craig
authors.forename: Keith D
authors.initials: KD
authors.lastname: Coon
authors.forename: Travis
authors.initials: T
authors.lastname: Dunckley
authors.forename: Daniel
authors.initials: D
authors.lastname: Bandy
authors.forename: Wendy
authors.initials: W
authors.lastname: Lee
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.forename: Diego
authors.initials: D
authors.lastname: Mastroeni
authors.forename: Andrew
authors.initials: A
authors.lastname: Grover
authors.forename: Rivka
authors.initials: R
authors.lastname: Ravid
authors.forename: Sigrid B
authors.initials: SB
authors.lastname: Sando
authors.forename: Jan O
authors.initials: JO
authors.lastname: Aasly
authors.forename: Reinhard
authors.initials: R
authors.lastname: Heun
authors.forename: Frank
authors.initials: F
authors.lastname: Jessen
authors.forename: Heike
authors.initials: H
authors.lastname: Kölsch
authors.forename: Joseph
authors.initials: J
authors.lastname: Rogers
authors.forename: Michael L
authors.initials: ML
authors.lastname: Hutton
authors.forename: Stacey
authors.initials: S
authors.lastname: Melquist
authors.forename: Ron C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Gene E
authors.initials: GE
authors.lastname: Alexander
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Caselli
authors.forename: Andreas
authors.initials: A
authors.lastname: Papassotiropoulos
authors.forename: Dietrich A
authors.initials: DA
authors.lastname: Stephan
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Huentelman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology / Q000473:pathology*; D001931:Brain Mapping; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009483:Neuropsychological Tests; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010750:Phosphoproteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D049268:Positron-Emission Tomography / Q000379:methods; D011506:Proteins / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D005904:Glial Fibrillary Acidic Protein; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011506:Proteins; C513637:WWC1 protein, human
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