A century-old tuberculosis vaccine is showing potential to retrain the immune system in older adults, offering a new biological explanation for links between the vaccine and a lower risk of Alzheimer’s disease. According to a study published in the journal Thehindu, researchers at the Massachusetts General Hospital examined whether the Bacillus Calmette-Guérin (BCG) vaccine could influence biological processes relevant to Alzheimer’s disease in humans.
Tuberculosis Vaccine Retrains Immune System and Alters Alzheimer’s Biomarkers
As the immune system ages, it enters a state of chronic, low-grade inflammation known as inflammaging. In the brain, this condition damages immune cells that normally clear toxic amyloid-beta, a protein that clumps together to form plaques characteristic of Alzheimer’s disease. Instead of clearing the protein, these cells become dysfunctional and fuel neuroinflammation.
The new study investigates trained immunity,
a phenomenon where certain vaccines provide innate immune cells with a long-lasting memory, making them more effective against unrelated threats. While antibodies recognize specific germs, trained immunity enables the innate immune system to respond more effectively to many different threats. Clinicians have long observed that bladder cancer patients treated with the BCG vaccine have a lower incidence of dementia.
Clinical Trial Design and Biomarker Findings
To test whether this immune training extends to the central nervous system, researchers at discovermagazine.com enrolled 23 adults aged 55 years and older. Roughly half of the participants showed characteristics of Alzheimer’s disease, while the other half were healthy.
Participants received two BCG doses administered a month apart through the skin. Researchers then tracked blood and cerebrospinal fluid samples periodically over the following year.
Across the blood-brain barrier, the cerebrospinal fluid shifted into a calming, regulatory state in all participants, showing no signs of runaway neuroinflammation. However, researchers observed a distinct difference in amyloid-beta biomarker levels between the two groups:
* Healthy Participants (Without Alzheimer’s Pathology): Amyloid levels declined significantly in the cerebrospinal fluid while increasing in blood samples over the 12-month period. * Participants With Established Alzheimer’s Pathology: This shift in amyloid levels did not materialize, indicating no measurable effect on protein clearance in this group.
Mahesh Chandra Kodali, a senior research fellow at Harvard Medical School and Massachusetts General Hospital, stated that the study suggests controlled mycobacterial immune stimulation can influence biological pathways related to Alzheimer’s disease.
Implications for Prevention and Future Research
The contrasting results between healthy participants and those with established disease suggest that the timing of administering the BCG vaccine might affect early disease dynamics and protein clearance from the central nervous system.
In participants with established Alzheimer’s, researchers attributed the lack of plaque-clearing activity to the brain’s ongoing inflammatory milieu, dementia-related cascades, a damaged blood-brain barrier, or dense amyloid plaques. In these environments, an already overwhelmed immune system has little capacity to respond, even if the immune cells have been retrained.
Dr. Basak noted that these factors dent the therapeutic appeal of BCG in patients who already have Alzheimer’s, while supporting its plausible utility as a preventive measure. Dr. Kodali emphasized that the trial was designed to understand the biology of BCG’s effects rather than to test whether it treats or prevents the disease.
Steven Arnold, managing director of the Interdisciplinary Brain Center at Mass General Brigham Neuroscience Institute, noted that the next step is to test the vaccine rigorously in larger, controlled studies. These future investigations will focus particularly on prevention, with the goal of preserving brain health before significant Alzheimer’s disease develops. Larger randomized clinical trials and longitudinal studies will also need to distinguish between prior BCG vaccination, latent or active tuberculosis infection, and Alzheimer’s disease progression.
