Objective:

To investigate the efficacy and safety of the anti-A3–10 monoclonal antibody 7B8 in APP/PS1 double-transgenic mice, focusing on its effects on amyloid clearance, neuroinflammation, and blood-brain barrier integrity, while assessing potential side effects.

Key Findings:

• 7B8 treatment significantly reduced cerebral Aβ deposition and improved cognitive function compared to the IgG group (P < 0.05).
• No increased risk of microhemorrhage was observed in the 7B8 group relative to controls (P > 0.05).
• 7B8 preserved vascular integrity and enhanced endothelial cell fluorescence intensity (P < 0.05).
• 7B8 upregulated vascular LRP-1 and BBB tight junction proteins while downregulating RAGE expression (P < 0.05).
• 7B8 suppressed neuroinflammatory markers and inhibited the HMGB-1/RAGE/NF-κB signaling pathway (P < 0.05).

Interpretation:

7B8 demonstrates potential as a safe and effective immunotherapy for Alzheimer's disease, alleviating cognitive impairment and protecting blood-brain barrier integrity without increasing microhemorrhage risk, suggesting a promising avenue for future therapies.

Limitations:

• Evaluation of CAA-related safety was limited to young mice, necessitating further studies in older models to fully understand the safety profile.

Conclusion:

7B8 is a promising candidate for Alzheimer's disease immunotherapy, providing insights into strategies that minimize amyloid-related imaging abnormalities.