{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T15:03:41Z","timestamp":1785164621519,"version":"3.55.0"},"reference-count":52,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Huntington's Disease"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>There is evidence for dysregulated cholesterol homeostasis in Huntington\u2019s disease (HD). The brain-specific cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-OHC) is decreased in manifest HD. 24(S)-OHC is an endogenous positive allosteric modulator (PAM) of the N-methyl-D-aspartate (NMDA) receptor, suggesting lower 24(S)-OHC may contribute to NMDA receptor hypofunction in HD. We hypothesized changes in 24(S)-OHC would be associated with cognitive impairment in early HD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To determine the interactions between oxysterols (24(S)-OHC, 25-OHC, and 27-OHC) at the NMDA receptor, the plasma levels of these oxysterols, and how these levels relate to cognitive performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      An\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      competition assay was used to evaluate interactions at the NMDA receptor, liquid chromatography coupled tandem mass spectrometry (LC-MS\/MS) was used to measure plasma 24(S)-OHC, 25-OHC, and 27-OHC levels, and correlation analyses investigated their relationship to performance on cognitive endpoints in TRACK and ENROLL-HD (NCT01574053).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      , 25-OHC and 27-OHC attenuated the PAM activity of 24(S)-OHC on the NMDA receptor. Lower plasma 24(S)-OHC levels and 24(S)\/25-OHC ratios were detected in participants with early HD. Moderate and consistent associations were detected between plasma 24(S)\/25-OHC ratio and performance on Stroop color naming, symbol digit modality, Trails A\/B, and emotion recognition. Little association was observed between the ratio and psychiatric or motor endpoints, suggesting specificity for the relationship to cognitive performance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our findings support growing evidence for dysregulated CNS cholesterol homeostasis in HD, demonstrate a relationship between changes in oxysterols and cognitive performance in HD, and propose that NMDA receptor hypofunction may contribute to cognitive impairment in HD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jhd-240030","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T10:45:48Z","timestamp":1725965148000},"page":"449-465","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Changes in 24(S)-Hydroxycholesterol Are Associated with Cognitive Performance in Early Huntington\u2019s Disease: Data from the TRACK and ENROLL HD Cohorts"],"prefix":"10.1177","volume":"13","author":[{"given":"Sarah M.","family":"Gray","sequence":"first","affiliation":[{"name":"Sage Therapeutics Inc","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Dai","sequence":"additional","affiliation":[{"name":"Sage Therapeutics Inc","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Sage Therapeutics Inc","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob T.","family":"Beckley","sequence":"additional","affiliation":[{"name":"Sage Therapeutics Inc","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Negah","family":"Rahmati","sequence":"additional","affiliation":[{"name":"Sage Therapeutics Inc","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Sage Therapeutics Inc","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Quirk","sequence":"additional","affiliation":[{"name":"Sage Therapeutics Inc","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200303030-00018"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7691"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.48.2.394"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16235"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2015.10.001"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-02232-6"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz298"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/scan\/nst029"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1509262112"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP280875"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20180135"},{"key":"e_1_3_3_13_2","first-page":"237","article-title":"Emotion recognition in Huntington\u2019s disease: A systematic review","volume":"36","author":"Henley SMD","year":"2012","unstructured":"Henley SMD, Novak MJU, Frost C, et al. 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