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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.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Corneveaux JJ,Liang WS,Reiman EM,Webster JA,Myers AJ,Zismann VL,Joshipura KD,Pearson JV,Hu-Lince D,Craig DW,Coon KD,Dunckley T,Bandy D,Lee W,Chen K,Beach TG,Mastroeni D,Grover A,Ravid R,Sando SB,Aasly JO,Heun R

doi

10.1016/j.neurobiolaging.2008.07.014

subject

Has Abstract

pub_date

2010-06-01 00:00:00

pages

901-9

issue

6

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(08)00258-3

journal_volume

31

pub_type

杂志文章

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