PT - JOURNAL ARTICLE AU - Meredith N. Braskie AU - Neda Jahanshad AU - Jason L. Stein AU - Marina Barysheva AU - Katie L. McMahon AU - Greig I. de Zubicaray AU - Nicholas G. Martin AU - Margaret J. Wright AU - John M. Ringman AU - Arthur W. Toga AU - Paul M. Thompson TI - Common Alzheimer's Disease Risk Variant Within the <em>CLU</em> Gene Affects White Matter Microstructure in Young Adults AID - 10.1523/JNEUROSCI.5794-10.2011 DP - 2011 May 04 TA - The Journal of Neuroscience PG - 6764--6770 VI - 31 IP - 18 4099 - http://www.jneurosci.org/content/31/18/6764.short 4100 - http://www.jneurosci.org/content/31/18/6764.full SO - J. Neurosci.2011 May 04; 31 AB - 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.