Association of common KIBRA variants with episodic memory and AD risk

Abstract

KIBRA SNP rs17070145 was identified in a GWAS of memory performance, with some but not all follow-up studies confirming association of its T allele with enhanced memory. This allele was associated with reduced Alzheimer's disease (AD) risk in one study, which also found © 2010 Elsevier Inc. All rights reserved.Correspondence: Nilüfer Ertekin-Taner, MD, PhD Address: Mayo Clinic Jacksonville, 4500 San Pablo Road, Birdsall 3 rd floor, Jacksonville, FL 32224 Phone: 904-953-8169 taner.nilufer@mayo.edu. * These authors contributed equally.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Supplemental NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript overexpression of KIBRA in memory-related brain regions of ADs. We genotyped rs17070145 and 14 additional SNPs in 2571 LOADs vs. 2842 controls, including African-Americans. We found significantly reduced risk for rs17070145 T allele in the older African-American subjects (p=0.007) and a suggestive effect in the older Caucasian series. Meta-analysis of this allele in >8000 subjects from our and published series showed a suggestive protective effect (p=0.07). Analysis of episodic memory in control subjects did not identify associations with rs17070145, though other SNPs showed significant associations in one series. KIBRA showed evidence of overexpression in the AD temporal cortex (p=0.06) but not cerebellum. These results suggest a modest role for KIBRA as a cognition and AD risk gene, and also highlight the multifactorial complexity of its genetic associations.

Acetylated Tau Obstructs KIBRA-Mediated Signaling in Synaptic Plasticity and Promotes Tauopathy-Related Memory Loss

“…Mice deficient in KIBRA have impaired hippocampal synaptic plasticity and memory deficits (Makuch et al, 2011). Intriguingly, KIBRA SNPs have been implicated in increased risk for late-onset AD (Burgess et al, 2011; Corneveaux et al, 2010; Rodriguez-Rodriguez et al, 2009). …”

Impact of KIBRA Polymorphism on Memory Function and the Hippocampus in Older Adults

“…A recent study provided evidence for better spatial memory especially in older T-allele carriers using a virtual reality navigation paradigm (Schuck et al, 2013). Also, a protective effect of T-allele carrier status for the risk of Alzheimer's disease has been observed in most, but not all investigated cohorts so far (Burgess et al, 2011;Corneveaux et al, 2010;Hayashi et al, 2010;Wang et al, 2013b).…”

Impact of Common KIBRA Allele on Human Cognitive Functions

“…A single-nucleotide polymorphism (SNP) in intron 9 of the KIBRA gene (common C-T substitution, rs17070145, GenBank accession number NM_015238) has recently been associated with episodic memory function and cognitive flexibility (Almeida et al, 2008;Bates et al, 2009;Nacmias et al, 2008;Papassotiropoulos et al, 2006;Schaper et al, 2008;Zhang et al, 2009;Schneider et al, 2010), and even with the risk of developing AD (Burgess et al, 2010;Corneveaux et al, 2008). The KIBRA protein is discussed to be involved in brain development and memory formation as a postsynaptic scaffold protein connecting cytoskeletal and signaling molecules (Johannsen et al, 2008;Yoshihama et al, 2009).…”