Bacillus Calmette-Guerin (BCG), a vaccine widely used to prevent tuberculosis and treat bladder cancer may also have properties that reduce the risk for dementia , according to new findings in a study of mice. BCG is a live, weakened vaccine made from an altered strain of the bacterium Mycobacterium bovis. The findings from this study, which was led by a team of Johns Hopkins Medicine researchers and funded by the National Institutes of Health, published today in Science Advances.
The researchers found that mice genetically engineered to have biological symptoms of dementia and that received the BCG vaccine were less likely to show hallmark signs of the disease, such as neurofibrillary (tau) tangles in the brain, sustained immune cell activation and memory loss compared to mice that received no vaccine.
"We're hard at work trying to understand the detailed mechanism for how it works, but this research points to early clues that aspects of trained immunity are likely driving this response," says William Bishai, M.D., Ph.D. , co-director of the Johns Hopkins Center for Tuberculosis Research .
Bishai explains that trained immunity refers to the ability of mammals' innate immune system cells — the usual "first responders" to threats like bacteria and viruses — to take on an expanded role. Following an initial stimulus, innate immune cells, often monocytes and macrophages, learn how to identify and respond to future threats that are different from the first. (Typically, other immune system cells, like T cells, take on this type of adaptive and learned response.)
In this case, Bishai believes that myeloid cells — innate immune cells — in the central nervous system and brain are using information from BCG to recognize and help the body respond to the formation of plaques and tangles characteristic of Alzheimer's disease and related dementias.
For this new study, Bishai and the researchers created a controlled experiment with mice with symptoms of dementia, specifically marked by tau pathology or a clumping of tau proteins in the brain representing late stages of the disease.
They divided mice into those that received the BCG vaccine and those that received a saline injection. An additional comparison group included age-matched mice that did not have dementia and that also received the saline injection.
