Brain-penetrant complement inhibition mitigates neurodegeneration in an Alzheimer's disease mouse model

Brain, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 29, 2024

Abstract Complement activation is implicated in driving brain inflammation, self-cell damage and progression of injury Alzheimer's disease other neurodegenerative diseases. Here, we investigate the impact delivery a complement-blocking antibody on neurodegeneration an mouse model. We engineered brain-penetrant recombinant targeting pro-inflammatory membrane attack complex. Systemic administration this APPNL-G-F mice reduced levels complement products, demonstrating successful entry target engagement. Prolonged treatment decreased synapse loss, amyloid burden inflammatory cytokine levels, concomitant with cognitive improvement compared to controls. These results underscore potential complement-inhibiting drugs as promising therapeutics, downstream plaques disease.

Language: Английский

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The schizophrenia-associated gene CSMD1 encodes a complement classical pathway inhibitor predominantly expressed by astrocytes and at synapses in mice and humans

Brain Behavior and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Knowing the enemy: strategic targeting of complement to treat Alzheimer disease

Nature Reviews Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Language: Английский

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Involvement of Complement in Alzheimer’s Disease: From Genetics Through Pathology to Therapeutic Strategies

Current topics in behavioral neurosciences, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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