BCG Vaccine Shows Early Potential to Influence Alzheimer's-Related Immune Markers: Study
USA: A pilot study suggests that the Bacillus Calmette-Guerin (BCG) vaccine, widely used to prevent tuberculosis, may influence immune responses and biomarkers associated with Alzheimer's disease.
Researchers found that BCG induced "trained immunity," altering immune cell behavior and Alzheimer's-related biomarkers in individuals without evidence of Alzheimer's pathology. While these findings are promising, larger randomized clinical trials are needed to determine whether BCG vaccination can help reduce the risk of cognitive decline or Alzheimer's disease.
The findings are from two one-year, open-label clinical trials published in Communications Medicine. The study, led by Marc S. Weinberg at Massachusetts General Hospital in Boston, USA, explored whether BCG-induced trained immunity extends to the central nervous system (CNS), potentially affecting biological pathways linked to Alzheimer's disease.
Immune aging is increasingly recognized as a contributing factor in Alzheimer's disease. Previous observational studies have suggested that BCG vaccination may lower the risk of developing Alzheimer's, but it remains uncertain whether the vaccine can produce long-lasting immune changes in the brain and spinal cord. The researchers therefore investigated immune responses in both the blood and cerebrospinal fluid (CSF) of older adults following BCG vaccination.
The study enrolled 23 adults aged 55 years or older at a single center. Twelve participants had no Alzheimer's-related pathology, while 11 had biological changes associated with the disease. Each participant received two intradermal BCG vaccinations administered one month apart and was followed for one year. Investigators monitored safety, cognitive outcomes, immune responses, and Alzheimer's-related biomarkers using blood samples, CSF analyses, cytokine assays, and single-cell immune profiling.
Key findings:
- BCG vaccination induced persistent trained immunity-like changes in immune cells within the cerebrospinal fluid, indicating long-lasting immune reprogramming in the central nervous system.
- Immune cells in the CSF showed enhanced innate immune responses and distinct gene expression patterns after vaccination.
- The immune changes observed in the CSF differed from those seen in blood, suggesting compartment-specific immune responses to BCG.
- In participants without Alzheimer's-related pathology, CSF amyloid-beta levels decreased while blood amyloid-beta levels increased following BCG vaccination.
- The observed amyloid-beta changes may indicate altered protein movement or clearance, although their clinical significance remains unclear.
- BCG vaccination was well tolerated, with no unexpected safety concerns reported during the one-year follow-up.
The authors said the findings provide preliminary evidence that BCG-induced trained immunity can occur within the central nervous system and may influence Alzheimer's-related pathways, highlighting its potential as an early intervention strategy. However, they cautioned that the exploratory study was limited by its small sample size, lack of a placebo control, and relatively homogeneous participant population.
They emphasized that larger, randomized, placebo-controlled trials are needed to confirm these findings and determine whether BCG vaccination can reduce the risk or progression of Alzheimer's disease.
Reference:
Weinberg, M. S., Kodali, M. C., Li, Z., Galler, J. A., Tidball, A. R., Reynolds, W. C., Young, C., Devitte-McKee, K., Fatima, H. A., Kivisäkk, P., Chatterjee, M., Kulkarni, A., Billingsly, J. M., Bartlett, A. L., Sui, S. H., Kühtreiber, W. M., Gerber, J., McManus, A. J., Tanzi, R. E., . . . Arnold, S. E. (2026). Bacillus Calmette–Guérin (BCG) immunotherapy reprograms CNS immunity and alters Alzheimer’s biomarkers: Results from two open-label clinical trials. Communications Medicine, 6(1), 358. https://doi.org/10.1038/s43856-026-01691-7
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