{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:01:46Z","timestamp":1789970506260,"version":"4.0.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Cognitive outcomes vary among individuals with cerebral small vessel disease (CSVD), and conventional imaging markers may not fully explain this heterogeneity. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is involved in TREM2-related myeloid responses, but the clinical significance of circulating sTREM2 in CSVD remains uncertain. We investigated the associations of serum sTREM2 with CSVD burden, white matter injury, and cognitive performance across different disease burdens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum sTREM2 levels were measured in 171 participants, including healthy controls and individuals with low- or high-burden CSVD. Associations between serum sTREM2 and total CSVD burden, individual imaging markers, white matter hyperintensity (WMH) volume, diffusion MRI measures, and cognitive performance were examined using multivariable regression models, tract-based spatial statistics, and burden-stratified analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum sTREM2 levels increased across the CSVD burden spectrum and were associated with WMH volume, whereas no significant associations were observed with lacunes, cerebral microbleeds, or enlarged perivascular spaces. Higher serum sTREM2 was associated with widespread increases in mean diffusivity across major white matter tracts, while fractional anisotropy abnormalities were limited. The association between serum sTREM2 and Montreal Cognitive Assessment (MoCA) performance differed according to CSVD burden (interaction \u03b2 = 0.462, HC3\n                      <jats:italic>P<\/jats:italic>\n                      = 0.027), with a positive burden-stratified association observed in high-burden CSVD. Interpretation: Serum sTREM2 exhibited a white matter\u2013predominant association pattern across the CSVD spectrum, and its relationship with cognitive performance varied according to disease burden. These findings suggest that circulating sTREM2 may provide additional information regarding biological heterogeneity in CSVD, although its cellular origin and longitudinal significance require further investigation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1937413","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:34:45Z","timestamp":1789968885000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Burden-dependent associations of serum sTREM2 with white matter injury and cognitive heterogeneity in cerebral small vessel disease"],"prefix":"10.3389","volume":"18","author":[{"given":"Qiuju","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianfeng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University","place":["Hefei, China"]},{"name":"Chobanian & Avedisian School of Medicine, Boston University","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongwu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1148\/radiol.12120319","article-title":"Mild cognitive impairment: Cerebrospinal fluid tau biomarker pathologic levels and longitudinal changes in white matter integrity.","volume":"266","author":"Amlien","year":"2013","journal-title":"Radiology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.jneuroim.2018.03.003","article-title":"Soluble TREM2 and biomarkers of central and peripheral inflammation in neurodegenerative disease.","volume":"319","author":"Bekris","year":"2018","journal-title":"J. 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