Premium
Alzheimer's disease risk variant in CLU is associated with neural inefficiency in healthy individuals
Author(s) -
Lancaster Thomas M.,
Brindley Lisa M.,
Tansey Katherine E.,
Sims Rebecca C.,
Mantripragada Kiran,
Owen Michael J.,
Williams Julie,
Linden David E.J.
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.10.012
Subject(s) - clusterin , functional magnetic resonance imaging , apolipoprotein e , disease , psychology , genome wide association study , neuroscience , medicine , genetics , biology , gene , genotype , single nucleotide polymorphism , apoptosis
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. Discussion 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.