Alzheimer's disease risk variant in CLU is associated with neural inefficiency in healthy individuals

• DOI: 10.1016/j.jalz.2014.10.012
• Publication Date: 2014-12-10T21:37:04Z
• Authors: Thomas M. Lancaster; Lisa M. Brindley; Katherine E. Tansey; Rebecca C. Sims; Kiran Mantripragada; Michael J. Owen; Julie Williams; David E.J. Linden
• Keywords: Clusterin; Apolipoprotein E; Genome-wide Association Study

Abstract Introduction Genome‐wide association studies identify rs11136000 in the CLU gene, which codes for Apolipoprotein J/Clusterin, as a significant risk variant Alzheimer's disease (AD). However, mechanisms by this confers susceptibility remain relatively unknown. Methods Eighty‐five healthy Caucasian participants underwent functional magnetic resonance imaging during working memory (WM) task and were genotyped rs11136000/ APOE loci. Results Here we show that young individuals with (C) have higher activation levels memory‐related prefrontal limbic areas WM task. We also found subtle reductions gray matter right hippocampal formation carriers of variant. Discussion suggest pattern multimodal results may reflect incipient structural differences inefficient activation. This study supports accumulating evidence suggesting genetic AD affects neural networks associated individuals.