{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:12:15Z","timestamp":1787022735323,"version":"build-2736575974"},"reference-count":58,"publisher":"Society for Neuroscience","issue":"19","license":[{"start":{"date-parts":[[2014,11,7]],"date-time":"2014-11-07T00:00:00Z","timestamp":1415318400000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2014,5,7]]},"abstract":"<jats:p>\n                    The C allele at the rs11136000 locus in the clusterin (\n                    <jats:italic>CLU<\/jats:italic>\n                    ) gene is the third strongest known genetic risk factor for late-onset Alzheimer's disease (LOAD). A recent genome-wide association study of LOAD found the strongest evidence of association with\n                    <jats:italic>CLU<\/jats:italic>\n                    at rs1532278, in high linkage disequilibrium with rs11136000. Brain structure and function are related to the\n                    <jats:italic>CLU<\/jats:italic>\n                    risk alleles, not just in LOAD patients but also in healthy young adults. We tracked the volume of the lateral ventricles across baseline, 1-year, and 2-year follow-up scans in a large sample of elderly human participants (\n                    <jats:italic>N<\/jats:italic>\n                    = 736 at baseline), from the Alzheimer's Disease Neuroimaging Initiative, to determine whether these\n                    <jats:italic>CLU<\/jats:italic>\n                    risk variants predicted longitudinal ventricular expansion. The rs11136000 major C allele\u2014previously linked with reduced\n                    <jats:italic>CLU<\/jats:italic>\n                    expression and with increased risk for dementia\u2014predicted faster expansion, independently of dementia status or\n                    <jats:italic>ApoE<\/jats:italic>\n                    genotype. Further analyses revealed that the\n                    <jats:italic>CLU<\/jats:italic>\n                    and\n                    <jats:italic>ApoE<\/jats:italic>\n                    risk variants had combined effects on both volumetric expansion and lateral ventricle surface morphology. The rs1532278 locus strongly resembles a regulatory element. Its association with ventricular expansion was slightly stronger than that of rs11136000 in our analyses, suggesting that it may be closer to a functional variant. Clusterin affects inflammation, immune responses, and amyloid clearance, which in turn may result in neurodegeneration. Pharmaceutical agents such as valproate, which counteract the effects of genetically determined reduced clusterin expression, may help to achieve neuroprotection and contribute to the prevention of dementia, especially in carriers of these\n                    <jats:italic>CLU<\/jats:italic>\n                    risk variants.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.5236-13.2014","type":"journal-article","created":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T13:38:19Z","timestamp":1399469899000},"page":"6537-6545","source":"Crossref","is-referenced-by-count":59,"title":["Combined Effects of Alzheimer Risk Variants in the\n                    <i>CLU<\/i>\n                    and\n                    <i>ApoE<\/i>\n                    Genes on Ventricular Expansion Patterns in the Elderly"],"prefix":"10.1523","volume":"34","author":[{"given":"Florence 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