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

Braskie, M. N., Jahanshad, N., Stein, J. L., Barysheva, M., McMahon, K. L., de Zubicaray, G. I., Martin, N. G., Wright, M. J., Ringman, J. M., Toga, A. W., & Thompson, P. 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), pp. 6764-6770.

View at publisher

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 CLUvariant 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.

Impact and interest:

89 citations in Scopus
Search Google Scholar™
83 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 85686
Item Type: Journal Article
Refereed: Yes
DOI: 10.1523/JNEUROSCI.5794-10.2011
ISSN: 1529-2401
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2011 The Authors
Deposited On: 01 Sep 2015 06:11
Last Modified: 01 Sep 2015 06:11

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page