We investigated the occurrence of a Cystatin C genetic variant in 312 Caucasian clinic-based Alzheimer's Disease (AD) cases versus 136 age-matched population-based Caucasian controls (age/age of onset range 60-91yrs). Logistic regression analyses revealed a significant 3-way interaction between APO-E e4 genotypes (APO-E4), CST3 G/G genotype and age/age of onset on AD diagnosis (p<.05) suggesting that the genetic risk changes differentially for APO-E or CST3 as a function of age. We stratified our sample based on age/age of onset of 80+yrs versus younger. In the younger group (231 cases; 86 controls) APOE4 conferred significant risk for AD (p<.0001) while CST3 genotype did not (p=.09). In the 80+ group (50 cases; 81 controls) APOE4 no longer conferred increased risk for AD (p=.26), while CST3 G/G became a significant risk factor (p=.014). No interaction was observed between APO-E and CST3. These data suggest that variation at the cystatin C gene is a novel risk factor for late onset Alzheimer's disease, particularly at an age when APO-E genotype no longer confers increased risk. Although no functional significance of the signal peptide variation has been reported at this time, it is likely that the variation confers risk for AD via interaction between cystatin C and A-beta exacerbating amyloidogenesis with subsequent cerebrovascular damage and dysfunction.
|Original language||English (US)|
|Number of pages||1|
|Journal||American Journal of Medical Genetics - Neuropsychiatric Genetics|
|State||Published - Aug 7 2000|
ASJC Scopus subject areas
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience