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Synaptic protein interactions were analyzed using a mesoscale proteomics assay. Immunocytochemistry was used to visualize synaptic proteins and \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazolepropionic acid receptor subunits. Neuronal function was measured with multi\u2010electrode arrays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Loss of\n                      <jats:italic>SORL1<\/jats:italic>\n                      expression significantly changes many synaptic protein\u2013protein interactions and patterns of expression.\n                      <jats:italic>SORL1\u2010<\/jats:italic>\n                      deficient neurons exhibit hyperactivity that is primarily amyloid beta independent.\n                      <jats:italic>SORL1<\/jats:italic>\n                      \u2010deficient neurons also have impaired network plasticity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings further support a growing body of literature implicating early endosomal recycling defects as drivers of AD pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71862","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:55:32Z","timestamp":1790060132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Alzheimer's disease risk gene\n                    <i>SORL1<\/i>\n                    is a regulator of excitatory neuronal function"],"prefix":"10.1002","volume":"22","author":[{"given":"C. Andrew","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"},{"name":"Institute for Stem Cell and Regenerative Medicine University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon E.","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"},{"name":"Institute for Stem Cell and Regenerative Medicine University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Stamenkovic","sequence":"additional","affiliation":[{"name":"Center for Integrative Brain Research Seattle Children's Research Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aquene N.","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"},{"name":"Institute for Stem Cell and Regenerative Medicine University of Washington School of Medicine  Seattle Washington USA"},{"name":"Department of Neurology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle J.","family":"Travaglini","sequence":"additional","affiliation":[{"name":"Allen Institute Brain Health  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen E. P.","family":"Smith","sequence":"additional","affiliation":[{"name":"Center for Integrative Brain Research Seattle Children's Research Institute  Seattle Washington USA"},{"name":"Graduate Program in Neuroscience University of Washington  Seattle Washington USA"},{"name":"Department of Pediatrics University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2106-0339","authenticated-orcid":false,"given":"Jessica E.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"},{"name":"Institute for Stem Cell and Regenerative Medicine University of Washington School of Medicine  Seattle Washington 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