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

doi:10.1016/j.jalz.2014.10.012

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

Department of Psychology

Cardiff University

Research output: Contribution to journal › Article › peer-review

29 Citations (SciVal)

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 language	English
Pages (from-to)	1144-1152
Number of pages	9
Journal	Alzheimer's & Dementia
Volume	11
Issue number	10
Early online date	10 Dec 2014
DOIs	https://doi.org/10.1016/j.jalz.2014.10.012
Publication status	Published - 31 Oct 2015

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10.1016/j.jalz.2014.10.012

Tom Lancaster
- tml45bath.acuk
- Department of Psychology - Senior Lecturer
Person: Research & Teaching

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title = "Alzheimer's disease risk variant in CLU is associated with neural inefficiency in healthy individuals",

abstract = "IntroductionGenome‐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.MethodsEighty‐five healthy Caucasian participants underwent functional magnetic resonance imaging during a working memory (WM) task and were genotyped for CLU rs11136000/APOE loci.ResultsHere 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.DiscussionWe 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.",

author = "Lancaster, {Thomas M.} and Brindley, {Lisa M.} and Tansey, {Katherine E.} and Sims, {Rebecca C.} and Kiran Mantripragada and Owen, {Michael J.} and Julie Williams and Linden, {David E.j.}",

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doi = "10.1016/j.jalz.2014.10.012",

language = "English",

volume = "11",

pages = "1144--1152",

journal = "Alzheimer's & Dementia ",

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TY - JOUR

T1 - Alzheimer's disease risk variant in CLU is associated with neural inefficiency in healthy individuals

AU - Lancaster, Thomas M.

AU - Brindley, Lisa M.

AU - Tansey, Katherine E.

AU - Sims, Rebecca C.

AU - Mantripragada, Kiran

AU - Owen, Michael J.

AU - Williams, Julie

AU - Linden, David E.j.

PY - 2015/10/31

Y1 - 2015/10/31

N2 - IntroductionGenome‐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.MethodsEighty‐five healthy Caucasian participants underwent functional magnetic resonance imaging during a working memory (WM) task and were genotyped for CLU rs11136000/APOE loci.ResultsHere 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.DiscussionWe 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.

AB - IntroductionGenome‐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.MethodsEighty‐five healthy Caucasian participants underwent functional magnetic resonance imaging during a working memory (WM) task and were genotyped for CLU rs11136000/APOE loci.ResultsHere 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.DiscussionWe 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.

U2 - 10.1016/j.jalz.2014.10.012

DO - 10.1016/j.jalz.2014.10.012

M3 - Article

SN - 1552-5260

VL - 11

SP - 1144

EP - 1152

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

IS - 10

ER -

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

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