Aim: 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 g/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 g/ml; p<0.05).
Conclusion: 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.