The Bacillus Calmette-Guérin vaccine reduces tau-related brain pathology, sustained inflammation, brain atrophy, and memory impairment in mice bred to show dementia-like symptoms, according to a preclinical study published in Science Advances by researchers at Johns Hopkins Medicine. Psychiatric Times reported that investigators tested the century-old tuberculosis vaccine to determine whether it offers protective benefits against neurodegenerative disease above and beyond what observational human data have previously suggested.
Microglial Clearance and Tau Tangle Reduction in PS19 Mice
Investigators focused their work on PS19 mice, a tauopathy-prone transgenic model that accumulates neurofibrillary tangles. Genetic Engineering and Biotechnology News noted that untreated mice in the control group showed activation of 716 genes connected to Alzheimer’s disease, cell death, and neuroinflammation, whereas BCG administration normalized all but nine of these genes. According to William Bishai, who serves as senior author of the study and co-director of the Johns Hopkins Center for Tuberculosis Research, microglial cells in the vaccinated mice displayed an enhanced capacity for phagocytosis.
Psychiatric Times reported that BCG vaccination led to reduced levels of deleterious activation, or microgliosis, among central nervous system microglial cells. Isolated microglia from vaccinated mice successfully engulfed and removed tau peptides. Drug Discovery News reported that brain monocyte recruitment from the periphery occurred at significantly higher levels in vaccinated animals, suggesting that recruited peripheral monocytes may augment the ability of endogenous microglial cells to clear tau tangles.
Immune mechanisms drive observed neurological changes
Researchers attribute these neurological changes to trained immunity rather than a generalized anti-inflammatory effect. Bishai noted in Psychiatric Times that microglial cells from the brains of vaccinated mice displayed a metabolic shift toward glycolysis, a hallmark of trained immunity. Investigators also observed higher levels of peripheral monocytes expressing the known trained immunity surface marker CD80.
Bioengineer.org reported that earlier animal research examined BCG in mouse models featuring amyloid-beta pathology, which represents an earlier disease stage marked by plaque formation. While amyloid-beta models showed higher levels of anti-inflammatory cytokines without reducing central nervous system lesion burden, the new tau model demonstrated an actual reduction in the tau neurofibrillary tangle burden.
Observational studies link vaccines to reduced dementia risk
Observational human studies have previously linked off-target effects of vaccines to a reduced incidence of dementia. Genetic Engineering and Biotechnology News reported that the shingles vaccine has been linked to a 20% reduced incidence of dementia. In addition, earlier investigations referenced by the study authors indicated that utilizing BCG as an immunotherapy treatment for non-muscle-invasive bladder cancer correlated with a decreased likelihood of developing dementia by 12% to 78% across durations lasting from three to 15 years.
Because BCG was first administered to a human infant in 1921 and is given to approximately 340 million infants annually, it possesses an extensive safety record. Psychiatric Times noted that no major obstacles prevent prospective clinical trials in humans. A clinical study is currently ongoing in Israel, and a United States-based consortium has proposed a large prospective trial to test the efficacy of BCG for preventing dementia in older, at-risk adults.
Frequently Asked Questions About BCG and Dementia Research
What bacterial strain is used to manufacture the BCG vaccine?
The BCG vaccine is a live, weakened vaccine made from an altered strain of the bacterium Mycobacterium bovis, as reported by Genetic Engineering and Biotechnology News.
How long does trained immunity induced by BCG typically last in humans?
Bishai stated in Psychiatric Times that trained immunity in humans has been shown to wane after about 12 months, raising the possibility that annual dosing could be necessary if BCG is ultimately developed as a human dementia vaccine.
Where was the primary preclinical study published?
Genetic Engineering and Biotechnology News reported that the findings appeared in the journal Science Advances under the title “BCG vaccination mitigates tau pathology and restores cognitive functions in PS19 mice.”
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