CLSTN2
Calsyntenin-2 precursor (Alcadein-gamma) (Alc-gamma) [CS2]
Publications[править]
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.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Atrophy
- Australia
- Calcium-Binding Proteins
- Cross-Sectional Studies
- Female
- Genetic Association Studies
- Genotyping Techniques
- Hippocampus
- Humans
- Intracellular Signaling Peptides and Proteins
- Longitudinal Studies
- Magnetic Resonance Imaging
- Male
- Membrane Proteins
- Memory Disorders
- Memory, Episodic
- Neuropsychological Tests
- Organ Size
- Phosphoproteins
- Polymorphism, Single Nucleotide
Keywords
- CLSTN2
- Episodic memory
- Gene–gene interactions
- Hippocampus
- KIBRA
Associations between genotypes and cognitive outcomes may provide clues as to which mechanisms cause individual differences in old-age cognitive performance. We investigated the effects of five polymorphisms on cognitive functioning in a population-based sample of 2,694 persons without dementia (60-102 years). A structural equation model (SEM) was fit to the cognitive data, yielding five specific latent factors (perceptual speed, episodic memory, semantic memory, category fluency, and letter fluency), as well as a global cognitive factor. These factors showed the expected associations with chronological age. Genotyping was performed for five single-nucleotide polymorphisms that have been associated with cognitive performance: APOE (rs429358), COMT (rs4680), BDNF (rs6265), KIBRA (rs17070145), and CLSTN2 (rs6439886). After controlling for age, gender, and education, as well as correcting for multiple comparisons, we observed negative effects of being an APOE ε4 carrier on episodic memory and perceptual speed. Furthermore, being a CLSTN2 TT carrier was associated with poorer semantic memory. For the global factor, the same pattern of results was observed. In addition, being a BDNF any A carrier was associated with better cognitive performance. Also, older age was associated with stronger genetic effects of APOE on global cognition. However, this interaction effect was partly driven by the presence of preclinical dementia cases in our sample. Similarly, excluding future dementia cases attenuated the effects of APOE on episodic memory and global cognition, suggesting that part of the effects of APOE on old-age cognitive performance may be driven by dementia-related processes.
MeSH Terms
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Cognition
- Female
- Genotype
- Humans
- Male
- Memory
- Middle Aged
- Polymorphism, Single Nucleotide
- Sweden
The role of the CLSTN2 (rs6439886) and KIBRA (rs17070145) SNPs in cognitive impairment was analysed in a 75-76 years old group. Various memory assessment tests were carried out on individuals at baseline and during follow-up investigations, and biallelic genotyping was performed. No influence of the allele status of either SNPs was observed on any memory test. No increased risk of any type of late development, and cognitive impairment was associated with rs6439886 or rs17070145.
MeSH Terms
- Aged
- Aging
- Alzheimer Disease
- Austria
- Calcium-Binding Proteins
- Cognitive Dysfunction
- Female
- Follow-Up Studies
- Genotype
- Humans
- Intracellular Signaling Peptides and Proteins
- Male
- Membrane Proteins
- Memory
- Neuropsychological Tests
- Phosphoproteins
- Polymorphism, Single Nucleotide
The kidney and brain expressed protein gene (KIBRA) and the calsyntenin 2 gene (CLSTN2) are reportedly involved in synaptic plasticity. Single nucleotide polymorphisms (SNPs) rs17070145 (KIBRA) and rs6439886 (CLSTN2) have been found to affect memory performance measures. This study examined the association of KIBRA SNP rs17070145 and CLSTN2 SNPs rs6439886 and rs17348572 (a nonsynonymous variant) with cognitive flexibility in 674 African Americans (AAs; 526 current smokers) and 419 European Americans (EAs; 318 current smokers). The subjects' cognitive flexibility was assessed using the Wisconsin Card Sorting Test. The effects on cognitive flexibility of sex, age, education, and tobacco recency (a possible mediator of gene effects in smokers), the three SNPs, and the interaction of each SNP with tobacco recency were analyzed using multivariate analysis of variance. In AAs, there were no main or interaction effects of the SNPs on cognitive flexibility. In EAs, the two CLSTN2 SNPs showed no main effect on cognitive flexibility. However, among EAs, individuals with the KIBRA rs17070145 T allele made significantly more perseverative responses (P=0.002) and perseverative errors (P=0.002) than those with no T allele. Furthermore, among EAs with the rs17070145 T allele, current smokers made significantly fewer perseverative responses (P<0.001) and perseverative errors (P<0.001) than past smokers. Nongenetic factors (age, education, and tobacco recency) had substantial effects on cognitive flexibility in both AAs and EAs. We conclude that variation in KIBRA influences cognitive flexibility in a population-specific way, and that current smoking status moderates this effect.
MeSH Terms
- Adult
- African Americans
- Aging
- Alleles
- Cognition
- Education
- European Continental Ancestry Group
- Female
- Humans
- Intracellular Signaling Peptides and Proteins
- Male
- Multivariate Analysis
- Neuropsychological Tests
- Phosphoproteins
- Polymorphism, Single Nucleotide
- Proteins
- Sequence Analysis, DNA
- Smoking
- Time Factors
- United States