The gamma-secretase complex is a multimeric aspartyl protease which plays a pivotal role in the production of amyloid beta-peptide, the main component of senile plaques in Alzheimer's disease (AD). APH-1a and APH-1b have been recently identified as important subunits of the gamma-secretase complex. We previously studied sequence variations in both genes and their association with AD in a small Italian population. The rare polymorphism c + 651T > G in APH-1b showed a possible interaction with the Apolipoprotein E (APOE) epsilon4 allele in the AD population sample. We extended our genetic analysis to 449 AD patients and 435 controls and, in AD cases, we found a significant interaction (P=0.001) between the allelic variants in the two genes, resulting in a marked increase of the relative risk for AD (OR=28.6). Despite the amino acid substitution does not seem to modify either the intracellular localization or the half-life of APH-1b protein, these data suggest that a cooperative mechanism involving APOE and APH-1b plays a role in the susceptibility to develop AD.
Interaction between the APOE epsilon4 allele and the APH-1b c+ 651T > G SNP in Alzheimer's disease / M. Poli, L. Benerini Gatta, C. Lovati, C. Mariani, D. Galimberti, E. Scarpini, I. Biunno, M. Musicco, R. Dominici, A. Albertini, D. Finazzi. - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - 29:10(2008 Oct), pp. 1494-1501. [10.1016/j.neurobiolaging.2007.03.019]
Interaction between the APOE epsilon4 allele and the APH-1b c+ 651T > G SNP in Alzheimer's disease
C. Lovati;C. Mariani;D. Galimberti;E. Scarpini;
2008
Abstract
The gamma-secretase complex is a multimeric aspartyl protease which plays a pivotal role in the production of amyloid beta-peptide, the main component of senile plaques in Alzheimer's disease (AD). APH-1a and APH-1b have been recently identified as important subunits of the gamma-secretase complex. We previously studied sequence variations in both genes and their association with AD in a small Italian population. The rare polymorphism c + 651T > G in APH-1b showed a possible interaction with the Apolipoprotein E (APOE) epsilon4 allele in the AD population sample. We extended our genetic analysis to 449 AD patients and 435 controls and, in AD cases, we found a significant interaction (P=0.001) between the allelic variants in the two genes, resulting in a marked increase of the relative risk for AD (OR=28.6). Despite the amino acid substitution does not seem to modify either the intracellular localization or the half-life of APH-1b protein, these data suggest that a cooperative mechanism involving APOE and APH-1b plays a role in the susceptibility to develop AD.File | Dimensione | Formato | |
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