{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:50:47Z","timestamp":1789019447397,"version":"build-2803163510"},"reference-count":79,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>\n                        PSEN1\n                        <jats:sup>E280A<\/jats:sup>\n                      <\/jats:italic>\n                      mutation causes autosomal dominant Alzheimer's disease (ADAD) with predictable onset, enabling presymptomatic studies. Extracellular vesicles (EVs) are emerging biomarkers of cognitive decline, but their role in early ADAD is unclear. The rare apolipoprotein E (\n                      <jats:italic>APOE3<\/jats:italic>\n                      ) Christchurch (\n                      <jats:italic>\n                        APOE3\n                        <jats:sup>Ch<\/jats:sup>\n                      <\/jats:italic>\n                      ) variant delays disease onset, yet its effect on EVs is unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We analyzed plasma EVs from mild cognitive impairment (MCI) and non\u2010MCI\n                      <jats:italic>\n                        PSEN1\n                        <jats:sup>E280A<\/jats:sup>\n                      <\/jats:italic>\n                      \u2010\n                      <jats:italic>APOE3<\/jats:italic>\n                      carriers and non\u2010MCI\n                      <jats:italic>\n                        PSEN1\n                        <jats:sup>E280A<\/jats:sup>\n                      <\/jats:italic>\n                      \u2010\n                      <jats:italic>\n                        APOE3\n                        <jats:sup>Ch<\/jats:sup>\n                      <\/jats:italic>\n                      carriers using flow cytometry, proteomics, and co\u2010culture assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      <jats:italic>\n                        APOE3\n                        <jats:sup>Ch<\/jats:sup>\n                      <\/jats:italic>\n                      \u2010EVs showed reduced vascular activation and inflammatory cargo linked to \u03b2\u2010catenin signaling, higher apoE levels, and enrichment in lipid\u2010loaded EVs. They mimicked the protective effect of recombinant ApoE3Ch on endothelial integrity by restoring \u03b2\u2010catenin nuclear localization. In contrast, EVs from non\u2010MCI\n                      <jats:italic>\n                        PSEN1\n                        <jats:sup>E280A<\/jats:sup>\n                      <\/jats:italic>\n                      \u2010\n                      <jats:italic>APOE3<\/jats:italic>\n                      carriers displayed vascular and inflammatory signatures associated with poorer cognition and detrimental astrocyte\u2013endothelium effects. These findings highlight\n                      <jats:italic>\n                        APOE3\n                        <jats:sup>Ch<\/jats:sup>\n                      <\/jats:italic>\n                      \u2010EVs as modulators of vascular and inflammatory pathways with biomarker and therapeutic potential in ADAD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71148","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T04:59:16Z","timestamp":1769057956000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Plasma extracellular vesicles from\n                    <i>APOE3<\/i>\n                    Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Lina","family":"Pineda\u2010Lopez","sequence":"first","affiliation":[{"name":"Grupo de 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