In genetically modified dementia pathology mice, it has been confirmed that the BCG vaccine used for tuberculosis prevention reduces the accumulation of abnormal brain proteins associated with dementia (tau proteins) and inflammation.

On the 22nd, a research team led by Dr. William Bishai of Johns Hopkins University reported in the scientific journal Science Advances that administering the BCG vaccine to genetically modified dementia mice reduced tau protein accumulation and inflammation in the brain while improving memory. They stated that this provides clues to elucidating the mechanism by which BCG affects dementia-related pathology.

Dr. Bishai noted, "BCG vaccine appears to reduce excessive inflammation in the brain, which is likely due to a trained immunity effect that expands the role of innate immune cells," adding, "We are currently studying other characteristics of trained immunity in the laboratory."

Recently, interest in the potential of vaccines for dementia prevention has grown as several preceding studies have linked the BCG vaccine and shingles vaccine to a lower risk of dementia.

The BCG vaccine group—used for tuberculosis prevention and immunotherapy for non-muscle-invasive bladder cancer—showed a 12% to 78% lower dementia incidence than the control group during a follow-up period of 3 to 15 years. The shingles vaccine was also associated with a 20% lower dementia incidence.

Focusing on the association between BCG vaccination and reduced dementia incidence, the research team conducted experiments using a genetically modified mouse model (PS19) that replicates tau protein abnormalities seen in Alzheimer's disease and other conditions to identify the underlying mechanism.

These mice were genetically modified to exhibit prominent tau pathology corresponding to the late stage of Alzheimer's disease, namely the aggregation of tau proteins in the brain.

BCG was administered three times at one-month intervals starting from 3 months of age, and major disease markers were evaluated around 8 to 10 months of age and compared with mice that did not receive the vaccine.

As a result, mice administered BCG showed a 5-fold higher probability of reduced tau protein deposition in the hippocampus—a brain region critical for memory formation—compared to the saline-administered control group, while the likelihood of showing persistent inflammatory markers was reduced to one-fourth.

The research team explained that this suggests immune cells may have already responded to tau proteins to clear some neurofibrillary tangles and form a stable or protective immune response.

MRI analysis showed mitigation of brain atrophy and ventricular enlargement in the mice, and in novel object recognition tests, BCG-administered mice showed improved ability to distinguish between previously seen objects and new objects.

The research team believes these effects are related to trained immunity. Trained immunity is a phenomenon where innate immune cells have their functions enhanced after receiving a specific stimulus, enabling them to react more effectively to subsequent different threats. This is a distinct concept from adaptive immunity, where immune cells recognize and respond to specific pathogens.

The research team stated that in mice administered BCG, the brain's immune cells showed an increased ability to clear tau protein aggregates, explaining that changes in the metabolic activity and function of immune cells may have allowed them to more efficiently remove tau proteins and reduce inflammation.

They added that further clarifying the mechanism by which BCG regulates immune cell responses to help clear tau proteins could help in developing new approaches for preventing dementia, such as Alzheimer's disease.

However, they emphasized that this study was conducted on mice and does not prove that the BCG vaccine prevents or treats dementia in humans. They stressed that it is necessary to further verify whether the vaccine induces the same immune changes in humans, whether it is effective for people at risk for dementia, and whether it can be safely applied.

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