Genetic variation in the interleukin-1 beta-converting enzyme associates with cognitive function. The PROSPER study.
S Trompet1, A J M de Craen, P Slagboom
1Department of Gerontology and Geriatrics, C-2-R, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. s.trompet@lumc.nl
Brain : a Journal of Neurology
|February 29, 2008
Summary
Genetic variations in the interleukin-1 beta-converting enzyme (ICE) gene are linked to better cognitive function in older adults. This suggests targeting ICE may help prevent age-related cognitive decline and memory loss.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Inflammation is implicated in age-related cognitive decline and dementia.
- The interleukin-1 (IL-1) signaling pathway, particularly IL-1 beta, may be a key factor.
- Interleukin-1 beta-converting enzyme (ICE) influences IL-1 beta levels, potentially impacting cognitive function.
Purpose of the Study:
- To investigate the association between genetic variations in the ICE gene and cognitive function in an elderly population.
- To determine if specific ICE gene polymorphisms correlate with IL-1 beta production and cognitive performance.
Main Methods:
- Genotyping of 5804 participants from the PROSPER study for four ICE gene polymorphisms (10643GC, 9323GA, 8996AG, 5352GA).
- Cross-sectional and longitudinal analyses using linear regression and linear mixed models to assess associations between polymorphisms, haplotypes, and cognitive function.
- Adjustments for covariates including age, sex, education, country, and pravastatin treatment.
Main Results:
- Carriers of the 10643C and 5352A alleles exhibited significantly lower IL-1 beta production.
- Homozygous carriers of the 10643C and 5352A alleles showed superior performance on executive function tests at baseline and follow-up.
- A haplotype combining 10643C and 5352A variants was associated with enhanced executive function; a similar trend was observed for memory function.
Conclusions:
- Genetic variation in the ICE gene is associated with improved cognitive function and reduced IL-1 beta levels.
- Lower IL-1 beta levels appear to be protective against memory and learning deficits.
- Inhibition of ICE presents a potential therapeutic strategy for preserving cognitive function in aging populations.
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