{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T14:39:00Z","timestamp":1763390340835,"version":"3.45.0"},"reference-count":71,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T00:00:00Z","timestamp":1763164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Econom\u00eda y Empresa","award":["SAF2017-89613R"],"award-info":[{"award-number":["SAF2017-89613R"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17-00275"],"award-info":[{"award-number":["PI17-00275"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The occurrence of amyloid-related imaging abnormalities (ARIAs), found in clinical trials for A\u03b2-immunotherapy, has been related to the antibody\u2019s effector function on glial activation by the Fc portion of the antibody. The use of single-chain variable fragments (scFv) has been proposed as a safer therapeutic strategy. Here, the effects of the mice format of bapineuzumap (mAb-m3D6) and its scFv (scFv-h3D6) on the occurrence of ARIAs in the APP23 mouse model of Alzheimer\u2019s disease (AD) and cerebral amyloid angiopathy (CAA) have been addressed by magnetic resonance imaging (MRI). Results are supported by histological and\/or biochemical determinations. Aged APP23 mice showed a significantly higher number of microhemorrhages than non-transgenic mice. mAb-m3D6 produced an increase in the number of new hemorrhagic events, mainly in the cortex, whereas scFv-h3D6 did not. Both mAb-m3D6 and scFv-h3D6 reduced A\u03b2 levels by the same extent. Axonal\/myelin damage was found in the frontal corpus callosum of APP23 mice, which did not recover after treatment. In conclusion, the scFv-h3D6 format appears safer than the full-length mAb in the APP23 model of AD and CAA. This finding is highly relevant in light of the new FDA- and EMA-approved mAbs, which exclude APOE\u03b54 allele carriers due to the occurrence of hemorrhages.<\/jats:p>","DOI":"10.3390\/biom15111602","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T14:04:07Z","timestamp":1763388247000},"page":"1602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ScFv-h3D6 Prevents Bapineuzumab-Induced Hemorrhagic Events in the APP23 Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8127-6425","authenticated-orcid":false,"given":"Silvia","family":"Lope-Piedrafita","sequence":"first","affiliation":[{"name":"Unitat de Biof\u00edsica, Departament de Bioqu\u00edmica i Biologia Molecular, Facultat de Medicina, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"},{"name":"Servei de Resson\u00e0ncia Magn\u00e8tica Nuclear, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red-Bioingenier\u00eda, Biomateriales y Nanomedicina (CIBER-BBN), Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Serra-Mir","sequence":"additional","affiliation":[{"name":"Protein Design and Immunotherapy Group, Departament de Bioqu\u00edmica i Biologia Molecular, Facultat de Bioci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Mel\u00f3n","sequence":"additional","affiliation":[{"name":"Protein Design and Immunotherapy Group, Departament de Bioqu\u00edmica i Biologia Molecular, Facultat de Bioci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1480-622X","authenticated-orcid":false,"given":"Anna","family":"Bonaterra","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Vall d\u2019Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8844-0091","authenticated-orcid":false,"given":"Mar","family":"Hern\u00e1ndez-Guillamon","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Vall d\u2019Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8644-4304","authenticated-orcid":false,"given":"Sandra","family":"Villegas","sequence":"additional","affiliation":[{"name":"Protein Design and Immunotherapy Group, Departament de Bioqu\u00edmica i Biologia Molecular, Facultat de Bioci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,15]]},"reference":[{"key":"ref_1","unstructured":"(2025, March 31). 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