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

Thomas M. Lancaster, Lisa M. Brindley, Katherine E. Tansey, Rebecca C. Sims, Kiran Mantripragada, Michael J. Owen, Julie Williams, David E.j. Linden

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Introduction
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.
Original languageEnglish
Pages (from-to)1144-1152
Number of pages9
JournalAlzheimer's & Dementia
Volume11
Issue number10
Early online date10 Dec 2014
DOIs
Publication statusPublished - 31 Oct 2015

Profiles

No photo of Thomas Lancaster

Thomas Lancaster

Person: Research & Teaching

Cite this

Lancaster, T. M., Brindley, L. M., Tansey, K. E., Sims, R. C., Mantripragada, K., Owen, M. J., Williams, J., & Linden, D. E. J. (2015). Alzheimer's disease risk variant in CLU is associated with neural inefficiency in healthy individuals. Alzheimer's & Dementia , 11(10), 1144-1152. https://doi.org/10.1016/j.jalz.2014.10.012