{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:03:24Z","timestamp":1779365004920,"version":"3.53.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      In brain, extracellular vesicles (EVs) play an essential role in the neuron\u2010glia interface and ensure the crosstalk between the brain and the periphery. Some studies now link the pathway dysfunction of the EVs to apolipoprotein E gene variant (\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54) and the risk of progression to Alzheimer's disease (AD). To better understand the role of\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 in pre\u2010clinical AD, we have determined levels of pathogenic, neurotrophic and inflammatory proteins in peripheral EVs (pEVs) and in plasma from cognitively impaired, no dementia (CIND) participants stratified upon the absence (\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\n                      <jats:sup>\u2010<\/jats:sup>\n                      ) or the presence (\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\n                      <jats:sup>+<\/jats:sup>\n                      ) of the \u03b54 allele of\n                      <jats:italic>APOE<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Levels of 15 neurodegenerative, neurotrophic and neuroinflammatory proteins were quantified in pEVs and compared to their plasma levels from cognitively normal and CIND participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Levels of neurotrophic and inflammatory markers were reduced in pEVs from\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\n                      <jats:sup>+<\/jats:sup>\n                      . The pentraxin\u20102\/\u03b1\u2010synuclein ratio measured in pEVs was able to predict AD 5 years before the onset among\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\n                      <jats:sup>+<\/jats:sup>\n                      \u2010CIND individuals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our findings suggest an alteration of the endosomal pathway in\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\n                      <jats:sup>+<\/jats:sup>\n                      and that pEVs pentraxin\u20102\/\u03b1\u2010synuclein ratio could serve as a useful early biomarker\u00a0for AD susceptibility.\n                    <\/jats:p>\n                  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