Researchers at the University of Texas Health Science Center at Houston administered the Bacillus Calmette-Guérin (BCG) vaccine to mouse models of Alzheimer's disease and examined its effects on the central nervous system.
The study found that BCG vaccination reprogrammed microglia, the brain's resident immune cells, shifting them toward a phenotype associated with reduced inflammation and enhanced clearance of amyloid-beta plaques.
Mice vaccinated before the onset of significant pathology showed markedly lower amyloid burden and improved cognitive performance in behavioral tests compared with unvaccinated controls.
The protective effect was largely absent when the vaccine was administered after amyloid accumulation was already advanced, indicating a critical window for intervention.
Single-cell RNA sequencing revealed that BCG induced lasting epigenetic changes in microglial precursors, altering their response to subsequent inflammatory signals.
The researchers also observed increased T-cell infiltration in the brain meninges following vaccination, suggesting systemic immune training influences the central nervous system.
While BCG has been used safely for decades against tuberculosis, its application for neurodegenerative disease would require extensive clinical testing in humans.
The authors caution that mouse models do not fully replicate human Alzheimer's disease and that the optimal timing, dosage, and long-term safety remain unknown.
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