{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T11:51:05Z","timestamp":1781783465448,"version":"3.54.5"},"reference-count":61,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Lions Alzheimer\u2019s Research Foundation"},{"name":"Alzheimer\u2019s Research Australia"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>CSF and blood soluble TREM2 (sTREM2) levels have been found to increase at early stage of Alzheimer's disease (AD). The relationships between sTREM2, AD-related biomarkers, and other neuroinflammation biomarkers remain unclear. Moreover, the impact of rare variants in TREM2 gene (R47H\/R62H), which are associated with increased risk of AD, on plasma sTREM2 has not been elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Investigate the association of plasma sTREM2 levels with brain amyloid-\u03b2 (A\u03b2) load and AD-related blood biomarkers, i.e., phosphorylated tau (pTau)-181, pTau-231, GFAP, NFL, and other neuroinflammation and peripheral inflammation markers in cognitively normal (CN) older adults at risk of AD (CN A\u03b2+) compared to CN A\u03b2-, including the effect of AD-linked TREM2 rare variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Plasma sTREM2 concentrations were measured by MesoScale Discovery (MSD) assay from the KARVIAH cohort. Participants underwent cognitive tests and PET amyloid imaging. Genetic data and blood biomarkers were included for correlation analysis. Associations with plasma sTREM2 were investigated upon stratification by PET-A\u03b2 load SUVR ((CN A\u03b2- (n\u2009=\u200965) and CN A\u03b2+ (n\u2009=\u200935)) as the main analysis. A subgroup analysis based on the\n                      <jats:italic toggle=\"yes\">TREM2 R47H<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">R62H<\/jats:italic>\n                      genotype was conducted as exploratory analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Plasma sTREM2 positively correlated with plasma pTau181, and pTau231 in CN A\u03b2+ group. Plasma sTREM2 positively correlated with serum microglial kynurenine pathway metabolites. Plasma sTREM2 and brain A\u03b2 load were higher in R47H TREM2 carriers compared to non-carriers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest plasma sTREM2 relates to downstream tau processes in amyloid-positive individuals, providing novel insights into the roles of peripheral TREM2 signaling that reflects microglial activity in early AD neuropathological development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251400780","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T16:23:58Z","timestamp":1765297438000},"page":"832-844","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma soluble TREM2 is associated with plasma pTau-181 and pTau-231 in cognitively normal older adults at risk of Alzheimer's disease"],"prefix":"10.1177","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1973-9628","authenticated-orcid":false,"given":"Prita R","family":"Asih","sequence":"first","affiliation":[{"name":"Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia"},{"name":"Alzheimer's Research Australia, Sarich Neuroscience Research Institute, Nedlands, WA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron W","family":"Morris","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA"},{"name":"Department of Neurology, Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 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