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Neuronal damage in early AD triggers tau release into central and peripheral systems. Despite influence from peripheral contributions, alterations in plasma total\u2010tau (T\u2010tau) remain valuable in indicating AD\u2010related neurodegeneration. Investigating relationships between SM metabolism and tau release during preclinical AD may uncover important biochemical processes and support advancing early non\u2010invasive detection and treatment approaches. This cross\u2010sectional study investigated cognitively unimpaired (CU) older adults from the KARVIAH cohort, grouped by cortical amyloid\u2010\u03b2 (A\u03b2) status through positron emission tomography (PET) imaging (CU A\u03b2\u2212 and CU A\u03b2+) and utilised a Biocrates\u2010targeted metabolomic platform and Single\u2010molecule array (Simoa) technology to quantify plasma levels of SMs and T\u2010tau, respectively. Associations between circulating SMs and T\u2010tau were examined within each group, with T\u2010tau\u2010associated SMs further evaluated for their association with cognitive performance and cortical A\u03b2 burden and their potential to discriminate CU A\u03b2+ from CU A\u03b2\u2212 individuals. Significant positive correlations were observed between SMs and T\u2010tau levels exclusively in CU A\u03b2+ individuals, suggesting connections between SM\u2010mediated biochemical pathways and tau release from early neurodegeneration in preclinical AD. Lower SM levels were associated with weaker working memory and executive function, as well as poorer global cognition, indicating their potential predictive value for weaker cognitive performance. Moreover, SMs were also inversely associated with cortical A\u03b2 load in CU A\u03b2+ individuals, possibly reflecting early SM\u2010mediated neuroprotective responses against AD pathogenesis. Receiver operating characteristic analysis further revealed the significant potential of the SM panel in distinguishing cortical PET\u2010A\u03b2 status and enhancing the predictive performance of plasma T\u2010tau in CU individuals. Therefore, circulating T\u2010tau\u2010associated SMs may serve as promising early biomarkers of lipid\u2010mediated processes in CU older adults with cortical amyloid pathology and tau\u2010related neurodegeneration.<\/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\/jnc70436-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.70436","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T06:10:17Z","timestamp":1778307017000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Circulating Sphingomyelins Correlate With Plasma T\u2010Tau in Cognitively Unimpaired Older Adults at Risk of Developing Alzheimer's Disease"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5496-0670","authenticated-orcid":false,"given":"Tahmida","family":"Sharmin","sequence":"first","affiliation":[{"name":"Macquarie Medical School Macquarie University  Macquarie Park New South Wales Australia"},{"name":"Department of Pharmacy University of Rajshahi  Rajshahi Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2863-0293","authenticated-orcid":false,"given":"James 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