title: Genetic association to the amyloid plaque associated protein gene COL25A1 in Alzheimer's disease.
abstract: The COL25A1 gene, located in 4q25, encodes the CLAC protein, which has been implicated in Alzheimer's disease (AD) pathogenesis. CLAC was originally identified in amyloid preparations from AD brain and has been shown to be associated with amyloid plaques, inhibition of Abeta-fibril elongation and increased protease resistance of Abeta-fibrils through direct binding to Abeta. These biochemical data as well as the genomic location of the COL25A1 gene in chromosome 4q25 where we previously have reported a weak linkage-signal in Swedish AD families encouraged us to perform a case-control association study of two LD blocks in COL25A1 using 817 AD cases and 364 controls. The LD blocks cover a putative Abeta-binding motif and the variable 3' end of the gene. The analyses indicated association to three of eight analysed SNPs. We found further support for the association by replication in a Swedish population-based longitudinal sample set (n=926). Thus, in addition to the biochemical data, there is now genetic evidence of association between COL25A1 and risk for Alzheimer's disease.
authors.affiliation: Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, KASPAC, Novum, S-141 57 Huddinge, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Forsell
authors.forename: Behnosh Fakhri
authors.initials: BF
authors.lastname: Björk
authors.forename: Lena
authors.initials: L
authors.lastname: Lilius
authors.forename: Karin
authors.initials: K
authors.lastname: Axelman
authors.forename: Susanne Froelich
authors.initials: SF
authors.lastname: Fabre
authors.forename: Laura
authors.initials: L
authors.lastname: Fratiglioni
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Caroline
authors.initials: C
authors.lastname: Graff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008137:Longitudinal Studies; D008297:Male; D024041:Non-Fibrillar Collagens / Q000235:genetics*; D058225:Plaque, Amyloid / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D013548:Sweden; D044465:White People / Q000235:genetics
chemical_list: C456021:COL25A1 protein, human; D024041:Non-Fibrillar Collagens