KIBRA and CLSTN2 polymorphisms exert interactive effects on human episodic memory

Preuschhof, Claudia; Heekeren, Hauke R.; Li, Shu-Chen; Sander, Thomas; Lindenberger, Ulman; Bäckman, Lars

doi:10.1016/j.neuropsychologia.2009.09.031

Cited by 66 publications

(73 citation statements)

References 78 publications

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“…Behaviorally, we confirmed previous findings of increased episodic memory performance in KIBRA T carriers (Papassotiropoulos et al, 2006;Bates et al, 2009;Preuschhof et al, 2010;Vassos et al, 2010). For the brain imaging data, Papassotiropoulos et al (2006) reported enhanced hippocampal activation in noncarriers of the T allele, but here, a genotype effect on hippocampal activation was seen in the opposite direction.…”

Section: Discussionsupporting

confidence: 90%

“…The T allele of a common KIBRA (WW and C2 domain containing 1) C/T polymorphism (rs17070145) was first linked to increased episodic memory performance in a genomewide association study and two independent replication samples by Papassotiropoulos and colleagues (2006). In subsequent studies, the T allele has been associated with increased episodic memory performance (Bates et al, 2009;Preuschhof et al, 2010;Vassos et al, 2010; but see Need et al, 2008).…”

Section: Introductionmentioning

confidence: 97%

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KIBRA Polymorphism Is Related to Enhanced Memory and Elevated Hippocampal Processing

Kauppi

Nilsson²,

Adolfsson³

et al. 2011

J. Neurosci.

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Several studies have linked the KIBRA rs17070145 T polymorphism to superior episodic memory in healthy humans. One study investigated the effect of KIBRA on brain activation patterns (Papassotiropoulos et al., 2006) and observed increased hippocampal activation in noncarriers of the T allele during retrieval. Noncarriers were interpreted to need more hippocampal activation to reach the same performance level as T carriers. Using large behavioral (N ϭ 2230) and fMRI (N ϭ 83) samples, we replicated the KIBRA effect on episodic memory performance, but found increased hippocampal activation in T carriers during episodic retrieval. There was no evidence of compensatory brain activation in noncarriers within the hippocampal region. In the main fMRI sample, T carriers performed better than noncarriers during scanning but, importantly, the difference in hippocampus activation remained after post hoc matching according to performance, sex, and age (N ϭ 64). These findings link enhanced memory performance in KIBRA T allele carriers to elevated hippocampal functioning, rather than to neural compensation in noncarriers.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 97%

KIBRA Polymorphism Is Related to Enhanced Memory and Elevated Hippocampal Processing

Kauppi

Nilsson²,

Adolfsson³

et al. 2011

J. Neurosci.

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“…The two SNPs were in Hardy-Weinberg equilibrium in both cohorts and the allele frequencies (Table 3) were similar to other Caucasian populations (e.g., Preuschhof et al, 2010).…”

Section: Genotypingsupporting

confidence: 70%

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

et al. 2015

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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 galley 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. AbstractThe variability of episodic memory decline and hippocampal atrophy observed with increasing age may partly be explained by genetic factors. KIBRA (kidney and brain expressed protein) and CLSTN2 (calsyntenin 2) are two candidate genes previously linked to episodic memory performance and volume of the hippocampus, a key memory structure.However, whether polymorphisms in these two genes also influence age-related longitudinal memory decline and hippocampal atrophy is still unknown. Using data from two independent cohorts, the Sydney Memory and Ageing Study and the Older Australian Twins Study, we investigated whether the KIBRA and CLSTN2 genetic polymorphisms (rs17070145, rs6439886) are associated with episodic memory performance and hippocampal volume in older adults (65-90 years at baseline). We were able to examine these polymorphisms in relation to memory and hippocampal volume using cross-sectional data and, more importantly, also using longitudinal data (2 years between testing occasions). Overall we did not find support for an association of KIBRA either alone or in combination with CLSTN2 with memory performance or hippocampal volume, nor did variation in these genes influence longitudinal memory decline or hippocampal atrophy in two cohorts of older adults.

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“…Given that complex phenotypes, such as memory, draw on multiple neurobiological substrates and are thus influenced by multiple genes (e.g., Bertolino et al, 2006;Markett et al, 2011;Nagel et al, 2008;Preuschhof et al, 2010), it is imperative to further investigate the resource-modulation hypothesis in relation to gene-gene interactions. Based on this consideration, and in light of the age-related decline in various preand postsynaptic components of the DA system (for reviews, see Bäckman et al, 2006Bäckman et al, , 2010, we investigated (i) whether genes relevant to pre-and postsynaptic components of the DA system contribute interactively to individual differences in episodic memory performance; and (ii) whether such interactive effects are magnified in old age.…”

Section: Introductionmentioning

confidence: 99%

Aging magnifies the effects of dopamine transporter and D2 receptor genes on backward serial memory

Papenberg

Nagel

et al. 2013

Neurobiology of Aging

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Aging compromises dopamine transporter (DAT) and receptor mechanisms in the frontostriatal circuitry. In a sample of 1288 younger and older adults, we investigated (i) whether individual differences in genotypes of the DAT gene (i.e., SLC6A3, the DAT variable number of tandem repeat 9/9, 9/10, and 10/10) and in the D2 receptor (DRD2) gene (i.e., the C957T [rs6277] CC and any T) interactively contribute to phenotype variations in episodic memory performance; and (ii) whether these genetic effects are magnified in older adults, because of considerable declines in the dopamine functions. Our results showed that carrying genotypes associated with higher levels of striatal synaptic dopamine (DAT 9/9) and higher density of extrastriatal D2 receptors (C957T CC) were associated with better backward serial recall, an episodic memory task with high encoding and retrieval demands. Critically, the gene-gene interaction effect was reliably stronger in older than in younger adults. In line with the resource modulation hypothesis, our findings suggest that aging-related decline in brain phenotypes (e.g., dopamine functions) could alter the relations between genotypes and behavioral phenotypes (e.g., episodic memory).

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KIBRA and CLSTN2 polymorphisms exert interactive effects on human episodic memory

Cited by 66 publications

References 78 publications

KIBRA Polymorphism Is Related to Enhanced Memory and Elevated Hippocampal Processing

KIBRA Polymorphism Is Related to Enhanced Memory and Elevated Hippocampal Processing

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

Aging magnifies the effects of dopamine transporter and D2 receptor genes on backward serial memory

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