Genetic association to the amyloid plaque associated protein gene COL25A1 in Alzheimer's disease

• Published in: Neurobiology of aging Vol. 31; no. 3; pp. 409 - 415
• Main Authors: Forsell, Charlotte, Björk, Behnosh Fakhri, Lilius, Lena, Axelman, Karin, Fabre, Susanne Froelich, Fratiglioni, Laura, Winblad, Bengt, Graff, Caroline
• Format: Journal Article
• Language: English
• Published: London Elsevier Inc 01.03.2010; Elsevier
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - genetics; Association study; Biological and medical sciences; Case-Control Studies; CLAC; COL25A1; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Development. Senescence. Regeneration. Transplantation; European Continental Ancestry Group - genetics; Female; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genetic Association Studies; Genotype; Haplotype association; Haplotypes; Humans; Internal Medicine; Linkage Disequilibrium; Longitudinal Studies; Male; Medical sciences; Medicin och hälsovetenskap; Neurology; Non-Fibrillar Collagens - genetics; Plaque, Amyloid - genetics; Polymorphism, Single Nucleotide; Population-based study; Sequence Analysis, DNA; SNP; Sweden; Vertebrates: nervous system and sense organs; Sweden; CLAC; SNP; COL25A1; Linkage disequilibrium; Association study; Population-based study; Haplotype association; Nervous system diseases; Senescence; Alzheimer disease; Protein; Cerebral disorder; Central nervous system disease; Degenerative disease; Amyloid
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2008.04.009

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 Aβ-fibril elongation and increased protease resistance of Aβ-fibrils through direct binding to Aβ. 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 Aβ-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.