Neural hyperactivation in carriers of the Alzheimer's risk variant on the clusterin gene

Eur Neuropsychopharmacol. 2011 Dec;21(12):880-4. doi: 10.1016/j.euroneuro.2011.02.001. Epub 2011 Mar 11.


Recent GWAS identified a risk variant for Alzheimer's disease (AD) at a locus (rs11136000) of the clusterin gene (CLU). Here we use functional magnetic resonance imaging (fMRI) during working memory to probe the effect of the risk variant on brain activation in healthy individuals. Participants with the CLU risk genotype had higher activity than participants with the protective allele in frontal and posterior cingulate cortex and the hippocampus, particularly during high memory demand. These results inform pathophysiological models of the preclinical progression of AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Clusterin / genetics*
  • Female
  • Genetic Variation / genetics*
  • Heterozygote*
  • Humans
  • Male
  • Memory / physiology
  • Middle Aged
  • Risk Factors
  • Young Adult


  • CLU protein, human
  • Clusterin