Aging and KIBRA/WWC1 genotype affect spatial memory processes in a virtual navigation task

Abstract

Spatial navigation relies on multiple mnemonic mechanisms and previous work in younger adults has described two separate types of spatial memory. One type uses directional as well as boundary-related information for spatial memory and mainly implicates the hippocampal formation. The other type has been linked to directional and landmark-related information and primarily involves the striatum. Using a virtual reality navigation paradigm, we studied the impacts of aging and a single nucleotide polymorphism (SNP rs17070145) of the KIBRA gene (official name: WWC1) on these memory forms. Our data showed that older adult's spatial learning was preferentially related to processing of landmark information, whereas processing of boundary information played a more prominent role in younger adults. Moreover, among older adults T-allele carriers of the examined KIBRA polymorphism showed better spatial learning compared to C homozygotes. Together these findings provide the first evidence for an effect of the KIBRA rs17070145 polymorphism on spatial memory in humans and age differences in the reliance on landmark and boundary-related spatial information.

Aging-related magnification of genetic effects on cognitive and brain integrity

“…In the human brain, KIBRA is mainly expressed in hippocampus and interacts with proteins involved in long-term potentiation, a cellular mechanism necessary for successful memory formation and consolidation [56]. In agreement with the resource-modulation hypothesis, a recent study reported that older adults carrying the KIBRA T allele showed better spatial learning compared with C-allele homozygotes, although no genotype effects were found in younger adults [57]. Another study also documented better episodic memory in older KIBRA T carriers than in C-allele homozygotes, but there was no effect of this polymorphism in a sample of older adults with mild cognitive impairment [58].…”

Genetics and Functional Imaging: Effects of APOE, BDNF, COMT, and KIBRA in Aging

“…A meta-analysis reported a reliable association between rs17070145 and episodic memory as well as working memory, explaining 0.5 and 0.1 % of variance, respectively (Milnik et al 2012; for review, see Schwab et al 2014). In line with the resource modulation hypothesis, a recent behavioral study reported that older adults carrying the T-allele showed better spatial learning compared to C homozygotes, whereas no genotype effects were found in younger adults (Schuck et al 2013). Interestingly, Almeida et al (2008) showed that better episodic memory for older KIBRA T-carriers, but there was no effect of this polymorphism in a sample of older adults with mild cognitive impairment.…”

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

“…Notably, in one study examining the effect of the KIBRA T-allele in a spatial navigation task, the reversed was observed. Older (60-70 years) T-allele carriers performed better than older CC-carriers but no such pattern was observed for younger (19-30 years) individuals (Schuck et al, 2013). Future studies should undertake a more detailed examination of the age-interaction with KIBRA or CLSTN2 status to clarify these relationships.…”