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Since the myelin sheath is highly enriched in lipids, changes in white matter (WM) microstructure observed via neuroimaging may reflect alterations in the myelin lipid profile. Given that the UF does not exist in rodents, its molecular properties are highly understudied. Therefore, we sought to quantify the phospholipid FA and cholesterol quantities of the human postmortem UF and evaluate any lipid\u2010related or myelin\u2010constituent gene\/protein changes associated with age and history of CA. UF samples were analyzed from individuals with depression who died by suicide with (DS\u2010CA) or without (DS) severe CA, and control individuals (CTRL), with an age span of 15 to 85\u2009years. Phospholipids were separated by thin\u2010layer chromatography; FAs and nonderivatized cholesterol were quantified by gas chromatography\u2010flame ionization detection. The relative expression of myelin\u2010constituent genes and proteins was measured by RT\u2010qPCR and immunoblotting, respectively. We found no robust relationships between CA or depression and lipid measures or myelin\u2010constituent gene\/protein levels. In contrast, phospholipids showed pronounced age effects that differed by fraction, with an overall trend of monounsaturated FAs increasing and long\u2010chain omega\u20106 polyunsaturated FAs decreasing with age. The expression of most myelin\u2010constituent genes and proteins declined with age; PLP1 and MAG showed significant decreases. Therefore, changes in lipid composition and lipid\u2010protein interactions likely contribute to age\u2010related myelin deficits and may in part underlie age\u2010associated cognitive decline.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70428-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70428","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:33:36Z","timestamp":1776674016000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Comprehensive Characterization of the Phospholipid and Cholesterol Composition of the Uncinate Fasciculus in the Human Brain: Evidence of Age\u2010Related Alterations"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2716-0712","authenticated-orcid":false,"given":"Kelly","family":"Perlman","sequence":"first","affiliation":[{"name":"McGill Group for Suicide Studies, Douglas Mental Health University Institute McGill University  Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1099-4198","authenticated-orcid":false,"given":"Chuck T.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mackenzie E.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Kim","sequence":"additional","affiliation":[{"name":"McGill Group for Suicide Studies, Douglas Mental Health University Institute McGill University  Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Turecki","sequence":"additional","affiliation":[{"name":"McGill Group for Suicide Studies, Douglas Mental Health University Institute McGill University  Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard P.","family":"Bazinet","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naguib","family":"Mechawar","sequence":"additional","affiliation":[{"name":"McGill Group for Suicide Studies, Douglas Mental Health University Institute McGill University  Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2019.00070"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.12.010"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1781(00)00171-2"},{"key":"e_1_2_11_5_1","article-title":"Myelin Lipid Metabolism and Its Role in Myelination and Myelin Maintenance","volume":"4","author":"Barnes\u2010V\u00e9lez J. 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