{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:21:35Z","timestamp":1789568495845,"version":"build-2803163510"},"reference-count":175,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T00:00:00Z","timestamp":1716595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["1RF1 AG058657"],"award-info":[{"award-number":["1RF1 AG058657"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["R01 AG084531-01"],"award-info":[{"award-number":["R01 AG084531-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a devastating disorder with a global prevalence estimated at 55 million people. In clinical studies administering certain anti-beta-amyloid (A\u03b2) antibodies, amyloid-related imaging abnormalities (ARIAs) have emerged as major adverse events. The frequency of these events is higher among apolipoprotein \u03b54 allele carriers (APOE4) compared to non-carriers. To reflect patients most at risk for vascular complications of anti-A\u03b2 immunotherapy, we selected an APPswe\/PS1dE9 transgenic mouse model bearing the human APOE4 gene (APPPS1:E4) and compared it with the same APP\/PS1 mouse model bearing the human APOE3 gene (APOE \u03b53 allele; APPPS1:E3). Using histological and biochemical analyses, we characterized mice at three ages: 8, 12, and 16 months. Female and male mice were assayed for general cerebral fibrillar and pyroglutamate (pGlu-3) A\u03b2 deposition, cerebral amyloid angiopathy (CAA), microhemorrhages, apoE and cholesterol composition, astrocytes, microglia, inflammation, lysosomal dysfunction, and neuritic dystrophy. Amyloidosis, lipid deposition, and astrogliosis increased with age in APPPS1:E4 mice, while inflammation did not reveal significant changes with age. In general, APOE4 carriers showed elevated A\u03b2, apoE, reactive astrocytes, pro-inflammatory cytokines, microglial response, and neuritic dystrophy compared to APOE3 carriers at different ages. These results highlight the potential of the APPPS1:E4 mouse model as a valuable tool in investigating the vascular side effects associated with anti-amyloid immunotherapy.<\/jats:p>","DOI":"10.3390\/ijms25115754","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T10:12:27Z","timestamp":1716804747000},"page":"5754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Temporal Characterization of the Amyloidogenic APPswe\/PS1dE9;hAPOE4 Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1113-8466","authenticated-orcid":false,"given":"Martine B.","family":"Grenon","sequence":"first","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Section Neuropsychology & Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7392-1069","authenticated-orcid":false,"given":"Maria-Tzousi","family":"Papavergi","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4031-8975","authenticated-orcid":false,"given":"Praveen","family":"Bathini","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3830-1779","authenticated-orcid":false,"given":"Martin","family":"Sadowski","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Psychiatry, and Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2983-7870","authenticated-orcid":false,"given":"Cynthia A.","family":"Lemere","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,25]]},"reference":[{"key":"ref_1","unstructured":"US Food and Drug Administration (2023, June 02). 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