Premium
P1–333: Genetic association to the novel CLAC gene in familial and clinic based Alzheimer's disease cases
Author(s) -
Forsell Charlotte,
Björk Behnosh F.,
Lilius Lena,
Axelman Karin,
Dillner Karin,
Fabre Susanne Froelich,
Winblad Bengt,
Graff Caroline
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.711
Subject(s) - senile plaques , linkage disequilibrium , single nucleotide polymorphism , pedigree chart , alzheimer's disease , genetic association , genetics , allele , family aggregation , disease , pathogenesis , medicine , gene , biology , pathology , genotype
Background: One of the main pathological hallmarks of Alzheimer’s disease (AD) is the senile plaques mainly consistent of insoluble deposits of the amyloid peptide (A ). A number of other components have been identified to co-localize with senile plaques in the brains of AD patients. Recently, the novel collagenous Alzheimer amyloid plaque component (CLAC) was described. It shows a specific binding to A , implicating involvement of CLAC in A fibrillization, proteolysis protection and A -mediated cytotoxicity. The gene encoding CLAC is located on chromosome band 4q24-25, in a region where we have observed increased allele sharing in Swedish AD pedigrees. Objective(s): To investigate the potential role of CLAC as a susceptibility gene for AD. Methods: Association studies in two AD populations were performed: one containing familial AD (FAD) cases, the other made up of cases from the Memory Clinic at Karolinska University Hospital. A third, population based sample set is under investigation. Results: We observed significant association in FAD cases to four single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium. Furthermore, the clinic based sample confirmed the association in two of the SNPs. Conclusions: Our results add genetic evidence to the previous experimental evidence for CLAC’s involvement in AD pathogenesis possibly by affecting the interaction between and CLAC.