BCG Vaccine Linked to Changes in Brain Immunity and Alzheimer’s Biomarkers

According to a small, year-long open-label clinical study, the Bacillus Calmette-Guérin (BCG) vaccine may alter immune activity around the brain and change levels of a protein closely associated with Alzheimer’s disease in older adults without evidence of the condition. However, the findings do not show that BCG prevents Alzheimer’s disease or slows its progression, but provide a possible biological explanation for previous studies linking BCG vaccination with a lower risk of developing the condition.

In the study, researchers from Mass General Brigham followed 23 adults aged 55 years and older over a 12-month period after they received BCG vaccination. Participants were divided into two groups: 12 participants without evidence of Alzheimer’s disease pathology and 11 participants with biomarkers indicating Alzheimer’s pathology. Since the study was open-label, both researchers and participants knew the vaccine had been administered, and there was no placebo comparison group.

Throughout the study, researchers collected blood samples and cerebrospinal fluid (CSF) to assess changes in immune activity and Alzheimer’s-related biomarkers. A key finding suggests BCG may increase the responsiveness of immune cells in both the blood and CSF when exposed to subsequent immune challenges. Importantly, this heightened immune activity did not coincide with increased inflammatory markers.

“This distinction matters because chronic inflammation in the brain is already thought to be part of Alzheimer’s disease biology. Inflammation can be helpful when it is short-lived and appropriately targeted, but when inflammatory signaling stays switched on over time, it can damage tissue and may contribute to disease progression,” says Marc Weinberg, MD, PhD, who contributed to the study while working as a research scientist at Mass General Brigham.