title: Alzheimer's disease risk variant in CLU is associated with neural inefficiency in healthy individuals.
abstract: BACKGROUND
  Genome-wide association studies identify rs11136000 in the CLU gene, which codes for Apolipoprotein J/Clusterin, as a significant risk variant for Alzheimer's disease (AD). However, the mechanisms by which this variant confers susceptibility remain relatively unknown.
  
  
  METHODS
  Eighty-five healthy Caucasian participants underwent functional magnetic resonance imaging during a working memory (WM) task and were genotyped for CLU rs11136000/APOE loci.
  
  
  RESULTS
  Here we show that young individuals with the CLU rs11136000 risk variant (C) have higher activation levels in memory-related prefrontal and limbic areas during a WM task. We also found subtle reductions in gray matter in the right hippocampal formation in carriers of the risk variant.
  
  
  CONCLUSIONS
  We suggest that this pattern of multimodal imaging results may reflect incipient structural differences and inefficient functional activation. This study supports accumulating evidence suggesting that genetic risk for AD affects the neural networks associated with memory in healthy individuals.
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK; Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff School of Medicine, Cardiff University, Cardiff, UK. Electronic address: LancasterTM@cardiff.ac.uk.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Lancaster
authors.affiliation: Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Brindley
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Tansey
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Sims
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Kiran
authors.initials: K
authors.lastname: Mantripragada
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Williams
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK; Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: David E J
authors.initials: DE
authors.lastname: Linden
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics*; D051152:Clusterin / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term; D008875:Middle Aged; D009415:Nerve Net; D012307:Risk Factors; D055815:Young Adult
chemical_list: C495242:CLU protein, human; D051152:Clusterin
keywords: Alzheimer's disease; CLU; DLPFC; Hippocampus; Imaging genetics; fMRI; rs11136000