Plasma Clusterin Levels and the rs11136000 Genotype in Individuals with Mild Cognitive Impairment and Alzheimer’s Disease

Gemma   M.   Mullan; Jane      McEneny; Marc      Fuchs; Cyril      McMaster; Stephen      Todd; Bernadette      McGuinness; Mark      Henry; A.   Peter   Passmore; Ian   S   Young; Janet   A.   Johnston

Abstract

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.

Keywords: Clusterin, rs 11136000, Mild cognitive impairment, Alzheimer’s disease.

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