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

Neuropsychologia. 2015 Nov;78:10-7. doi: 10.1016/j.neuropsychologia.2015.09.031. Epub 2015 Sep 28.


The 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 and 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.

Keywords: CLSTN2; Episodic memory; Gene–gene interactions; Hippocampus; KIBRA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / genetics
  • Aging / pathology
  • Aging / psychology
  • Atrophy / genetics
  • Australia / epidemiology
  • Calcium-Binding Proteins / genetics*
  • Cross-Sectional Studies
  • Female
  • Genetic Association Studies
  • Genotyping Techniques
  • Hippocampus / pathology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Membrane Proteins / genetics*
  • Memory Disorders / epidemiology
  • Memory Disorders / genetics
  • Memory Disorders / pathology
  • Memory, Episodic*
  • Neuropsychological Tests
  • Organ Size
  • Phosphoproteins / genetics*
  • Polymorphism, Single Nucleotide*


  • CLSTN2 protein, human
  • Calcium-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Phosphoproteins
  • WWC1 protein, human