BCG vaccine linked to changes in brain immunity and Alzheimer's biomarkers

• In older adults, the BCG vaccine may enhance the responsiveness of immune cells in the cerebrospinal fluid and blood, suggesting it may strengthen immune function without triggering harmful inflammation.
• Among those without evidence of Alzheimer’s disease, beta-amyloid levels decreased in cerebrospinal fluid and increased in the bloodstream, which may indicate improved clearance of beta-amyloid from the brain.
• However, the vaccine did not produce similar effects in those who already had biomarker evidence of Alzheimer’s disease, suggesting BCG may be more effective before significant disease develops.
• This small, open-label study provides a possible explanation for previous links between BCG and Alzheimer’s risk, but larger trials are still necessary.

The Bacillus Calmette-Guérin (BCG) vaccine prevents severe forms of tuberculosis (TB) and is the world’s most widely used vaccine, as well as the oldest vaccine still in use.

In recent years, researchers have become increasingly interested in its “off-target” effects, which may extend beyond protection against TB.

Previous research suggests that BCG may strengthen the body’s broader immune response, known as trained immunity.

Most research has focused on immune changes in the bloodstream, while it remains unclear whether BCG can also influence immune cells within the central nervous system (CNS).

Now, a small, year-long clinical study suggests the 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.

The findings, published in Communications Medicine, 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.