Lecanemab blocks the effects of the Aβ/fibrinogen complex on blood clots and synapse toxicity in organotypic culture
Proteinaceous brain inclusions, neuroinflammation, and vascular dysfunction are common pathologies in Alzheimer's disease (AD). Vascular deficits include a compromised blood-brain barrier, which can lead to extravasation of blood proteins like fibrinogen into the brain. Fibrinogen's interaction with the amyloid-beta (Aβ) peptide is known to worsen thrombotic and cerebrovascular pathways in AD. Lecanemab, an FDA-approved antibody therapy for AD, clears Aβ plaque from the brain and slows cognitive decline. Here, we show that lecanemab blocks fibrinogen's binding to Aβ protofibrils, preventing Aβ/fibrinogen-mediated delayed fibrinolysis and clot abnormalities in vitro and in human plasma. Additionally, we show that lecanemab dissociates the Aβ/fibrinogen complex and prevents fibrinogen from exacerbating Aβ-induced synaptotoxicity in mouse organotypic hippocampal cultures. These findings reveal a possible protective mechanism by which lecanemab may slow disease progression in AD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:121 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 121(2024), 17 vom: 23. Apr., Seite e2314450121 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Singh, Pradeep Kumar [VerfasserIn] |
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| Links: |
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| Themen: |
12PYH0FTU9 |
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| Anmerkungen: |
Date Completed 17.04.2024 Date Revised 28.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2314450121 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 100 | 1 | |a Singh, Pradeep Kumar |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Lecanemab blocks the effects of the Aβ/fibrinogen complex on blood clots and synapse toxicity in organotypic culture |
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| 520 | |a Proteinaceous brain inclusions, neuroinflammation, and vascular dysfunction are common pathologies in Alzheimer's disease (AD). Vascular deficits include a compromised blood-brain barrier, which can lead to extravasation of blood proteins like fibrinogen into the brain. Fibrinogen's interaction with the amyloid-beta (Aβ) peptide is known to worsen thrombotic and cerebrovascular pathways in AD. Lecanemab, an FDA-approved antibody therapy for AD, clears Aβ plaque from the brain and slows cognitive decline. Here, we show that lecanemab blocks fibrinogen's binding to Aβ protofibrils, preventing Aβ/fibrinogen-mediated delayed fibrinolysis and clot abnormalities in vitro and in human plasma. Additionally, we show that lecanemab dissociates the Aβ/fibrinogen complex and prevents fibrinogen from exacerbating Aβ-induced synaptotoxicity in mouse organotypic hippocampal cultures. These findings reveal a possible protective mechanism by which lecanemab may slow disease progression in AD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Alzheimer’s disease | |
| 650 | 4 | |a amyloid-beta | |
| 650 | 4 | |a fibrinogen | |
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| 700 | 1 | |a Simões-Pires, Elisa Nicoloso |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zu-Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Torrente, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Calvano, Marissa |e verfasserin |4 aut | |
| 700 | 1 | |a Sharma, Anurag |e verfasserin |4 aut | |
| 700 | 1 | |a Strickland, Sidney |e verfasserin |4 aut | |
| 700 | 1 | |a Norris, Erin H |e verfasserin |4 aut | |
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