Common Alzheimer's disease risk variant within the CLU gene affects white matter microstructure in young adults

Braskie, Meredith N., Jahanshad, Neda, Stein, Jason L., Barysheva, Marina, McMahon, Katie L., de Zubicaray, Greig I., Martin, Nicholas G., Wright, Margaret J., Ringman, John M., Toga, Arthur W. and Thompson, Paul M. (2011) Common Alzheimer's disease risk variant within the CLU gene affects white matter microstructure in young adults. The Journal of Neuroscience, 31 18: 6764-6770. doi:10.1523/JNEUROSCI.5794-10.2011

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Author Braskie, Meredith N.
Jahanshad, Neda
Stein, Jason L.
Barysheva, Marina
McMahon, Katie L.
de Zubicaray, Greig I.
Martin, Nicholas G.
Wright, Margaret J.
Ringman, John M.
Toga, Arthur W.
Thompson, Paul M.
Title Common Alzheimer's disease risk variant within the CLU gene affects white matter microstructure in young adults
Formatted title
Common Alzheimer's disease risk variant within the CLU gene affects white matter microstructure in young adults
Journal name The Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
1529-2401
Publication date 2011-05-04
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.5794-10.2011
Open Access Status File (Publisher version)
Volume 31
Issue 18
Start page 6764
End page 6770
Total pages 7
Place of publication Washington, DC, U.S.A.
Publisher Society for Neuroscience
Collection year 2012
Language eng
Formatted abstract
There is a strong genetic risk for late-onset Alzheimer's disease (AD), but so far few gene variants have been identified that reliably contribute to that risk. A newly confirmed genetic risk allele C of the clusterin (CLU) gene variant rs11136000 is carried by ∼88% of Caucasians. The C allele confers a 1.16 greater odds of developing late-onset AD than the T allele. AD patients have reductions in regional white matter integrity. We evaluated whether the CLU risk variant was similarly associated with lower white matter integrity in healthy young humans. Evidence of early brain differences would offer a target for intervention decades before symptom onset. We scanned 398 healthy young adults (mean age, 23.6 ± 2.2 years) with diffusion tensor imaging, a variation of magnetic resonance imaging sensitive to white matter integrity in the living brain. We assessed genetic associations using mixed-model regression at each point in the brain to map the profile of these associations with white matter integrity. Each C allele copy of the CLU variant was associated with lower fractional anisotropy—a widely accepted measure of white matter integrity—in multiple brain regions, including several known to degenerate in AD. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. Young healthy carriers of the CLU gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing AD later in life.

Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
School of Psychology Publications
Centre for Advanced Imaging Publications
 
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Created: Mon, 16 May 2011, 15:45:27 EST by Sandrine Ducrot on behalf of Centre for Advanced Imaging