AI Article Synopsis
- Alzheimer's disease (AD) is characterized by protein-rich brain inclusions, neuroinflammation, and problems with blood vessels, which includes a weakened blood-brain barrier that allows blood proteins like fibrinogen to enter the brain.
- Fibrinogen interacts negatively with the amyloid-beta (Aβ) peptide, worsening blood clotting issues and blood flow in AD.
- Lecanemab, an FDA-approved antibody for AD, shows potential to reduce Aβ levels and slow cognitive decline by blocking the harmful interaction between Aβ and fibrinogen, preventing further damage in the brain.
Article 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 (Aβ) peptide is known to worsen thrombotic and cerebrovascular pathways in AD. Lecanemab, an FDA-approved antibody therapy for AD, shows promising results in facilitating reduction of Aβ from the brain and slowing cognitive decline. Here we show that lecanemab blocks fibrinogen's binding to Aβ protofibrils, normalizing Aβ/fibrinogen-mediated delayed fibrinolysis and clot abnormalities 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10827200 | PMC |
| http://dx.doi.org/10.1101/2024.01.20.576458 | DOI Listing |
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