Common Alzheimer's Disease Risk Variant Within the CLU Gene Affects White Matter Microstructure in Young Adults
Year: 2011
Type: article
Study design: Observational Study
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.
Source: Journal of Neuroscience
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Achievement Rewards for College Scientists Foundation, National Institutes of Health, University of California, Los Angeles, Medical Research Council, National Health and Medical Research Council, National Institute on Aging, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, National Institute of Child Health and Human Development, U.S. National Library of Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1121515656, G1372278137, G1734661113, G1951096767, G199256479, G2382774797, G2392088378, Genetic influences on the brain: A twin imaging study, G2594996237, G3109596333, G3157495676, G3199409182, G3495954047, G3544081313, G3553261625, G399895291, Studying the Genetic Basis of Schizophrenia through Tract Alterations, G4741411087, G5018145102, G519183068, G5244094983, Computational Modeling of High-Field MR Images, G5850931412, G5938296382, G6460849299, G651483984, Genetics of moliness, G7928560463, G9000166586, G9000179559, G9000264890, Training Grant in Neurobehavioral Genetics
OpenAlex ID: W1533914007