title: Plasma clusterin levels and the rs11136000 genotype in individuals with mild cognitive impairment and Alzheimer's disease.
abstract: OBJECTIVE
  Substantial evidence links atherosclerosis and Alzheimer's disease (AD). Apolipoproteins, such as apolipoprotein E, have a causal relationship with both diseases. The rs11136000 SNP within the CLU gene, which encodes clusterin (apolipoprotein J), is also associated with increased AD risk. The aim of this study was to investigate the relationship between plasma clusterin and the rs11136000 genotype in mild cognitive impairment (MCI) and AD.
  
  
  METHODS
  Plasma and DNA samples were collected from control, MCI and AD subjects (n=142, 111, 154, respectively). Plasma clusterin was determined by ELISA and DNA samples were genotyped for rs11136000 by TaqMan assay.
  
  
  RESULTS
  Plasma clusterin levels were higher in MCI and AD subjects vs. controls (222.3 ± 61.3 and 193.6 ± 58.2 vs. 178.6 ± 52.3 μg/ml, respectively; p<0.001 for both comparisons), and in MCI vs. AD (p<0.05). Plasma clusterin was not influenced by genotype in the MCI and AD subjects, although in control subjects plasma clusterin was lower in the TT vs. TC genotypes (157.6 ± 53.4 vs. 188.6 ± 30.5 μg/ml; p<0.05).
  
  
  CONCLUSIONS
  This study examined control, MCI and AD subjects, identifying for the first time that plasma clusterin levels were influenced, not only by the presence of AD, but also the transitional stage of MCI, while rs11136000 genotype only influenced plasma clusterin levels in the control group. The increase in plasma clusterin in MCI and AD subjects may occur in response to the disease process and would be predicted to increase binding capacity for amyloid-beta peptides in plasma, enhancing their removal from the brain.
authors.affiliation: Centre for Public Health, Queen's University Belfast, Institute of Pathology, Grosvenor Road, Belfast BT12 6BJ, Northern. Ireland. j.mceneny@qub.ac.uk.
authors.forename: Gemma M
authors.initials: GM
authors.lastname: Mullan
authors.forename: Jane
authors.initials: J
authors.lastname: McEneny
authors.forename: Marc
authors.initials: M
authors.lastname: Fuchs
authors.forename: Cyril
authors.initials: C
authors.lastname: McMaster
authors.forename: Stephen
authors.initials: S
authors.lastname: Todd
authors.forename: Bernadette
authors.initials: B
authors.lastname: McGuinness
authors.forename: Mark
authors.initials: M
authors.lastname: Henry
authors.forename: A Peter
authors.initials: AP
authors.lastname: Passmore
authors.forename: Ian S
authors.initials: IS
authors.lastname: Young
authors.forename: Janet A
authors.initials: JA
authors.lastname: Johnston
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics*; D051152:Clusterin / Q000097:blood* / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000097:blood / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D051152:Clusterin