Lecanemab blocks the effects of the Aß/fibrinogen complex on blood clots and synapse toxicity in organotypic culture.
Proc Natl Acad Sci U S A
; 121(17): e2314450121, 2024 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-38621133
ABSTRACT
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 (Aß) peptide is known to worsen thrombotic and cerebrovascular pathways in AD. Lecanemab, an FDA-approved antibody therapy for AD, clears Aß plaque from the brain and slows cognitive decline. Here, we show that lecanemab blocks fibrinogen's binding to Aß protofibrils, preventing Aß/fibrinogen-mediated delayed fibrinolysis and clot abnormalities in vitro and in human plasma. Additionally, we show that lecanemab dissociates the Aß/fibrinogen complex and prevents fibrinogen from exacerbating Aß-induced synaptotoxicity in mouse organotypic hippocampal cultures. These findings reveal a possible protective mechanism by which lecanemab may slow disease progression in AD.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombose
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Doença de Alzheimer
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Anticorpos Monoclonais Humanizados
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article