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Vascular proteins, including fibrinogen, extravasate into the brain, further contributing to damage and inflammation. Fibrinogen's interaction with A\u03b2 is well\u2010established, but how this interaction contributes to synaptic dysfunction in AD is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Organotypic hippocampal cultures (OHC) were exposed to A\u03b242 oligomers, fibrinogen, or A\u03b242\/fibrinogen complexes. Synaptotoxicity was analyzed by Western blot. A\u03b242 oligomers, fibrinogen, or their complexes were intracerebroventricularly injected into mice. Histopathological AD markers, synaptotoxicity, neuroinflammation, and vascular markers were observed by Western blot and immunofluorescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>A\u03b242\/fibrinogen complexes led to synaptic loss, tau181 phosphorylation, neuroinflammation, and BBB disruption, independent of Mac1\/CD11b receptor signaling. Blocking A\u03b242\/fibrinogen complex formation prevented synaptotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings indicate that the A\u03b242\/fibrinogen complex has a synergistic impact on hippocampal synaptotoxicity and neuroinflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Fibrinogen binds to the central region of A\u03b2, forming a plasmin\u2010resistant complex.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The A\u03b2\/fibrinogen complex induces synaptotoxicity, inflammation, and BBB disruption.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Synaptotoxicity induced by the complex is independent of Mac1 receptor signaling.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70119","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:40:05Z","timestamp":1746751205000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Synergistic effects of the A\u03b2\/fibrinogen complex on synaptotoxicity, neuroinflammation, and blood\u2013brain barrier damage in Alzheimer's disease models"],"prefix":"10.1002","volume":"21","author":[{"given":"Elisa Nicoloso","family":"Sim\u00f5es\u2010Pires","sequence":"first","affiliation":[{"name":"Patricia and John Rosenwald Laboratory of Neurobiology and Genetics 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