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A newly confirmed genetic risk allele C of the clusterin (\n                    <jats:italic>CLU<\/jats:italic>\n                    ) gene variant rs11136000 is carried by \u223c88% 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\n                    <jats:italic>CLU<\/jats:italic>\n                    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 \u00b1 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\n                    <jats:italic>CLU<\/jats:italic>\n                    variant was associated with lower fractional anisotropy\u2014a widely accepted measure of white matter integrity\u2014in 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\n                    <jats:italic>CLU<\/jats:italic>\n                    gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing AD later in life.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.5794-10.2011","type":"journal-article","created":{"date-parts":[[2011,5,4]],"date-time":"2011-05-04T13:01:28Z","timestamp":1304514088000},"page":"6764-6770","source":"Crossref","is-referenced-by-count":152,"title":["Common Alzheimer's Disease Risk Variant Within the\n                    <i>CLU<\/i>\n                    Gene Affects White Matter Microstructure in Young Adults"],"prefix":"10.1523","volume":"31","author":[{"given":"Meredith N.","family":"Braskie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda","family":"Jahanshad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason L.","family":"Stein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Barysheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie L.","family":"McMahon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greig I.","family":"de Zubicaray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas G.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret J.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Ringman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur W.","family":"Toga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2011,5,4]]},"reference":[{"key":"2023041303502042000_31.18.6764.1","doi-asserted-by":"crossref","unstructured":"Bartzokis G (2009) Alzheimer's disease as homeostatic responses to age-related myelin breakdown. 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