Journal
NEUROBIOLOGY OF AGING
Volume 29, Issue 10, Pages 1494-1501Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2007.03.019
Keywords
Alzheimer's disease; APH-1; APOE; single nucleotide polymorphism; gamma-secretase; beta-arnyloid
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Funding
- M.I.U.R. PRIN 2002
- University of Brescia
- Fondazione Monzino and Associazione Amici del Centro Dino Ferrari
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The gamma-secretase complex is a multimeric aspartyl protease which plays a pivotal role in the production of amyloid P-peptide, the main component of senile plaques in Alzheimer's disease (AD). APH-1a and APH-1b have been recently identified as important sub-units 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) epsilon 4 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 play, a role in the susceptibility to develop AD. (C) 2007 Elsevier Inc. All rights reserved.
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