Researchers at Mass General Brigham have found that the Bacillus Calmette-Guerin (BCG) vaccine, developed a century ago to prevent tuberculosis, can remodel immune cells surrounding the brain and shift Alzheimer's disease biomarkers. The findings, published in Communications Medicine, offer a biological explanation for previous observations linking BCG vaccination to lower Alzheimer's risk.
How BCG affects the brain
The yearlong clinical trial studied older adults with and without biomarker evidence of Alzheimer's pathology. In participants free of the disease, BCG promoted increased responsiveness in immune cells in the cerebrospinal fluid — a trained immunity effect previously observed in other tissues. The vaccine also shifted levels of amyloid-beta, a key Alzheimer's biomarker, lowering it in cerebrospinal fluid while raising it in the bloodstream over 12 months.
Timing matters
In participants who already had Alzheimer's pathology, BCG showed no measurable effect on amyloid levels, suggesting the vaccine's window of benefit may be in early or pre-symptomatic stages. This timing-dependent effect could influence how doctors think about deploying immune-modulating therapies for neurodegenerative disease.
From TB vaccine to brain therapy
BCG is one of the most widely administered vaccines in history, typically given at birth in countries with high tuberculosis rates. If larger trials confirm its neuroprotective effects, it could offer a low-cost, readily available intervention for Alzheimer's prevention, particularly in regions where amyloid-targeting drugs remain unaffordable or inaccessible.