Dokument: Lecanemab Binds to Transgenic Mouse Model‐Derived Amyloid‐β Fibril Structures Resembling Alzheimer's Disease Type I, Type II and Arctic Folds
| Titel: | Lecanemab Binds to Transgenic Mouse Model‐Derived Amyloid‐β Fibril Structures Resembling Alzheimer's Disease Type I, Type II and Arctic Folds | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=69976 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250624-122943-9 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Peralta Reyes, Fernanda S. [Autor] Sommerhage, Simon [Autor] Willbold, Dieter [Autor] Schröder, Gunnar F. [Autor] Gremer, Lothar [Autor] | |||||||
| Dateien: |
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| Stichwörter: | lecanemab, immunogold-EM, tg-mouse models, cryo-EM structures, Alzheimer's disease, ARIA-E, amyloid-beta | |||||||
| Beschreibung: | Aims: Lecanemab, an Alzheimer’s disease US Food and Drug Administration-approved monoclonal antibody, was previously reported to have a high affinity against intermediately sized amyloid-β aggregates. Subsequently, it was observed by immunogold labelling that lecanemab can also bind to human type I amyloid-β fibrils. To determine whether lecanemab binds to amyloid-β fibril structures other than type I, we analysed its binding capacity to various structurally defined and pathologically relevant amyloid-β fibrils.
Methods: We performed immunogold labelling with lecanemab on extracted amyloid-β fibril preparations from six different Alzheimer´s disease mouse models whose structures were previously solved by cryo-EM and quantified the relative binding affinities of lecanemab to the different fibril polymorphs. Results: Our results show that lecanemab exhibits high binding affinity to amyloid-β fibril structures that have a flexible N-terminus in common, as is the case for type I, type II and murine type III amyloid-β fibril polymorphs, which resemble or are identical to human structures observed in sporadic and familial cases of Alzheimer’s disease, including a case with the Arctic (E22G) mutation. In contrast, only weak lecanemab binding was observed for murine amyloid-β fibrils with a fixed and ordered N-terminus. Conclusions: These findings may also explain the low incidence of ARIA-E with lecanemab in clinical trials. This is because human meningeal amyloid-β fibrils derived from cerebral amyloid angiopathy affected brain tissue also contain a fixed and ordered N-terminus, most likely preventing lecanemab binding. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Peralta Reyes, F. S., Sommerhage, S., Willbold, D., Schröder, G., & Gremer, L. (2025). Lecanemab Binds to Transgenic Mouse Model‐Derived Amyloid‐β Fibril Structures Resembling Alzheimer’s Disease Type I, Type II and Arctic Folds. Neuropathology and Applied Neurobiology, 51(3), Article e70022. https://doi.org/10.1111/nan.70022 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 24.06.2025 | |||||||
| Dateien geändert am: | 24.06.2025 |
