{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:21:59Z","timestamp":1791915719795,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:00:00Z","timestamp":1775865600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;amp;D Transl Res &amp;amp; Clin Interv"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>The disruption of key mechanisms involved in amyloid beta (A\u03b2) clearance during the early stages of dementia may contribute to the progression of cognitive decline toward irreversible brain damage. In this study, we investigated multiple immune\u2010related pathways implicated in the management and clearance of A\u03b2 within circulating extracellular vesicles (cEVs) and serum from individuals with subjective cognitive decline (SCD) who later progressed to mild cognitive impairment (MCI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      A cytokine panel and the levels of A\u03b2\n                      <jats:sub>1\u201342<\/jats:sub>\n                      were quantified in both cEVs and serum from a longitudinally followed cohort of elderly with SCD, using mesoscale and Luminex technologies. We investigated associations with A\u03b2 burden, cognitive performance,\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 allele status, and the likelihood of conversion to MCI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      In SCD patients, the concentrations of A\u03b2\n                      <jats:sub>1\u201342<\/jats:sub>\n                      and macrophage\u2010colony stimulating factor (M\u2010CSF) were higher, respectively, in cEVs and serum. No difference was observed for fraktaline, interleukin (IL)\u20104, IL\u201013, interferon gamma (IFN\u2010\u03b3), and sCD40L in either cEVs or serum between SCD and control patients. Based on receiver operating characteristic curve analysis, regression modeling, and correlations with cognitive performance, M\u2010CSF levels in serum effectively distinguished individuals with SCD who converted to MCI from those who remained stable. Interestingly, combining M\u2010CSF and cEVs A\u03b2\n                      <jats:sub>1\u201342<\/jats:sub>\n                      with the Rey Auditory Verbal Learning Test (RAVLT) cognitive scores provided an excellent classification for SCD converted to MCI up to 2 years prior to clinical diagnosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      Our findings support the potential value of integrating serum M\u2010CSF levels with RAVLT performance and cEVs A\u03b2\n                      <jats:sub>1\u201342<\/jats:sub>\n                      concentrations into a multimodal biomarker panel for longitudinal monitoring of progressive neurocognitive impairment.\n                    <\/jats:p>\n                  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