A vaccine widely used to prevent tuberculosis may also influence the brain's immune environment and Alzheimer's-related biomarkers, according to a year-long clinical study published in Communications Medicine.
Researchers at Mass General Brigham found that the Bacillus Calmette-Guérin (BCG) vaccine enhanced immune responses and altered amyloid-beta biomarkers in older adults without evidence of Alzheimer's disease. The changes were not observed in participants who already showed biological signs of the disease.
The study involved 23 adults aged 55 years and older, including 12 participants without Alzheimer's pathology and 11 with biomarker evidence of the disease. Researchers collected blood and cerebrospinal fluid samples at regular intervals over one year following BCG vaccination.
Immune Changes Extend Beyond Tuberculosis Protection
The researchers found that BCG increased the responsiveness of immune cells to subsequent immune challenges, indicating broader effects on immune function beyond tuberculosis protection.
Unlike many immune-stimulating therapies, the heightened immune activity was not accompanied by an increase in inflammatory markers, which are associated with neurodegeneration.
"The immune system and the brain may be far more connected than we once thought," said senior and co-corresponding author Steven Arnold, managing director of the Interdisciplinary Brain Center at Mass General Brigham Neuroscience Institute.
"The next step is to test this rigorously in larger, controlled studies, particularly in prevention, where the hope would be to preserve brain health before significant Alzheimer's disease develops," Arnold said.
Early Alzheimer's Biomarkers Shift, But Larger Trials Needed
Among participants without Alzheimer's pathology, researchers observed a significant decline in amyloid-beta levels in cerebrospinal fluid alongside an increase in amyloid-beta levels in blood over the 12-month study period.
The researchers said the shift could indicate changes in how amyloid proteins move from the central nervous system into the bloodstream. No comparable changes were detected in participants with Alzheimer's pathology, suggesting the vaccine may have greater effects before disease-related changes become established.
"Vaccines have traditionally been viewed through the lens of infectious disease prevention," said co-first author Marc Weinberg, who conducted the research at Mass General Brigham and is now an employee of AbbVie.
"Although more research is needed, these findings suggest they may also influence biological processes involved in brain aging and neurodegenerative disease," Weinberg said.
The study builds on earlier research suggesting BCG may produce "trained immunity," a long-lasting enhancement of the body's innate immune response that has previously been linked to protection against unrelated infections and lower Alzheimer's risk.
The authors cautioned that the trial was open-label, involved only 23 participants, and did not include a placebo group. They also noted that the findings apply to BCG vaccination in older adults and do not address the effects of routine childhood vaccination used in many countries where tuberculosis remains common.
The researchers said larger randomized, placebo-controlled studies will be needed to determine whether the biological changes observed after BCG vaccination can reduce the risk of Alzheimer's disease or slow its development.
