WWC1 genotype modulates age-related decline in episodic memory function across the adult life span.

John Muse, Matthew Emery, Fabio Sambataro, Herve Lemaitre, Hao-Yang Tan, Qiang Chen, Bhaskar S. Kolachana, Saumitra Das, Joseph H. Callicott, Daniel R. Weinberger, Venkata S. Mattay
Biological Psychiatry. 2014-05-01; 75(9): 693-700
DOI: 10.1016/j.biopsych.2013.09.036

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Comment in
Biol Psychiatry. 2014 May 1;75(9):674-5.

BACKGROUND: Episodic memory (EM) declines with age and the rate of decline is
variable across individuals. A single nucleotide polymorphism (rs17070145) in the
WWC1 gene that encodes the KIBRA protein critical for long-term potentiation and
memory consolidation has previously been associated with EM performance, as well
as differences in hippocampal engagement during EM tasks using functional
magnetic resonance imaging (fMRI). In the current study, we explore the effect of
this polymorphism on EM-related activity and cognitive performance across the
adult life span using fMRI.
METHODS: Two hundred thirty-two healthy, Caucasian subjects (18-89 years)
completed a battery of cognitive tests, as well as an EM task during an fMRI
RESULTS: WWC1 T carriers had significantly better delayed recall performance than
CC individuals (p = .006). The relationship between increasing age and recall
scores (immediate and delayed) was also significantly different between WWC1
genotype groups (p = .01). In addition to the age-related decline in hippocampal
formation (HF) activation (p < .05; false discovery ratesmall volume
correction-HF-region of interest), we observed an age by WWC1 genotype
interaction on HF activation during encoding and retrieval. The CC group showed a
significant negative association between HF activity and increasing age, while no
such association was observed in the T carrier group (left HF p = .04; r-z
correlation difference during encoding and retrieval; right HF p = .0008; r-z
correlation difference during retrieval).
CONCLUSIONS: Our results show a dynamic relationship between rs17070145
polymorphism and increasing age on neuronal activity in the hippocampal region.

© 2013 Society of Biological Psychiatry Published by Society of Biological
Psychiatry All rights reserved.


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