{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:59:15Z","timestamp":1785430755079,"version":"3.56.0"},"posted":{"date-parts":[[2026,2,11]]},"group-title":"Neuroscience","reference-count":73,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["T32 AG071745"],"award-info":[{"award-number":["T32 AG071745"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["S100 D034435"],"award-info":[{"award-number":["S100 D034435"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30 CA051008"],"award-info":[{"award-number":["P30 CA051008"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Toulmin Award"],"award-info":[{"award-number":["Toulmin Award"]}],"id":[{"id":"https:\/\/ror.org\/00hjz7x27","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Anti-A\u03b2 immunotherapies for Alzheimer\u2019s Disease (AD) have high rates of amyloid-related imaging abnormalities (ARIA), an adverse side effect with markedly higher rates in\n                  <jats:italic>APOE4<\/jats:italic>\n                  carriers. We developed a mouse model of ARIA centered on human\n                  <jats:italic>APOE3<\/jats:italic>\n                  and\n                  <jats:italic>APOE4<\/jats:italic>\n                  genotypes with amyloidosis (5xFAD transgene) and microglia tagged with green fluorescent protein (from the CX3CR1 promoter). We measured acute changes following a single intravenous treatment with 3D6 anti-A\u03b2 immunotherapy. Across 82 mice,\n                  <jats:italic>APOE4<\/jats:italic>\n                  mice showed stepwise reductions in the number of plaques from one to ten days, with significant reductions in the subiculum (48%) and thalamus (40%) at ten days. There was no significant reduction in\n                  <jats:italic>APOE3<\/jats:italic>\n                  mice. There was a concomitant significant increase in deposition of cerebral amyloid angiopathy (CAA) in\n                  <jats:italic>APOE4<\/jats:italic>\n                  mice at one (76%) and three (51%) days in leptomeningeal vessels. The increased CAA correlated with a significant 189% increase in A\u03b2 within microglia of\n                  <jats:italic>APOE4<\/jats:italic>\n                  (but not\n                  <jats:italic>APOE3<\/jats:italic>\n                  ) mice at one day. Smooth muscle actin staining showed significant 58% reduction near CAA. MRI analysis revealed a significant 32% increase in microhemorrhages ten days following treatment. These data demonstrate an\n                  <jats:italic>APOE4<\/jats:italic>\n                  -specific redistribution of parenchymal amyloid to CAA by 3D6 within days, leading to increased vascular damages associated with ARIA.\n                <\/jats:p>","DOI":"10.64898\/2026.02.09.704876","type":"posted-content","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T23:50:12Z","timestamp":1770853812000},"source":"Crossref","is-referenced-by-count":0,"title":["Intravenous anti-A\u03b2 immunotherapy acutely increases cerebral amyloid angiopathy and vascular damages in APOE4 mice"],"prefix":"10.64898","author":[{"given":"Philip","family":"Pikus","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd, NW, Washington DC, 20007 USA"},{"name":"Interdisciplinary Program in Neuroscience, Georgetown University, 3970 Reservoir Rd, NW, Washington DC, 20007 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gracie S.","family":"Healey","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd, NW, Washington DC, 20007 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Biology, Department of Biology, Georgetown University, Washington, DC, 37th and O St, NW, Washington DC, 20057 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgi","family":"Shautidze","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Georgetown University Medical Center, 3900 Reservoir Rd, NW, Washington DC, 20007 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Siddapureddy","sequence":"additional","affiliation":[{"name":"Department of Biology, Department of Biology, Georgetown University, Washington, DC, 37th and O St, NW, Washington DC, 20057 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichien","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oncology, Georgetown Lombardi Comprehensive Cancer Center, 3800 Reservoir Rd, NW, Washington DC, 20007 USA"},{"name":"Center for Translational Imaging, Georgetown Lombardi Comprehensive Cancer Center, 3800 Reservoir Rd, NW, Washington DC, 20007 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Albanese","sequence":"additional","affiliation":[{"name":"Department of Oncology, Georgetown Lombardi Comprehensive Cancer Center, 3800 Reservoir Rd, NW, Washington DC, 20007 USA"},{"name":"Center for Translational Imaging, Georgetown Lombardi Comprehensive Cancer Center, 3800 Reservoir Rd, NW, Washington DC, 20007 USA"},{"name":"Department of Radiology, Georgetown Lombardi Comprehensive Cancer Center, 3800 Reservoir Rd, NW, Washington DC, 20007 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Oncology, Georgetown Lombardi Comprehensive Cancer Center, 3800 Reservoir Rd, NW, Washington DC, 20007 USA"},{"name":"Center for Translational Imaging, Georgetown Lombardi Comprehensive Cancer Center, 3800 Reservoir Rd, NW, Washington DC, 20007 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Scott","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Georgetown University Medical Center, 3800 Reservoir Rd, NW, Washington DC, 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6276-248X","authenticated-orcid":false,"given":"G. William","family":"Rebeck","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd, NW, Washington DC, 20007 USA"},{"name":"Interdisciplinary Program in Neuroscience, Georgetown University, 3970 Reservoir Rd, NW, Washington DC, 20007 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