A vaccine made more than a hundred years ago to fight tuberculosis cut the amount of tangled tau protein in the brains of mice bred to develop it, according to a new study described in Psychiatric Times on October 30, 20261. Tau tangles are twisted protein fibers that build up inside nerve cells in Alzheimer’s disease and related dementias. The vaccine is called BCG, short for Bacillus Calmette-Guérin1.
The work was led by William R. Bishai, a physician and tuberculosis researcher1. In an interview, he said the vaccine’s long safety record leaves no real obstacles to testing it in people going forward1. The results so far are in mice only.
What the researchers did
The team used PS19 mice, a strain bred to build up tau in the brain, a condition called tauopathy1. These mice start to show symptoms at 6 to 7 months of age1. The researchers gave them BCG at 3 months, which Bishai described as the start of young adulthood in mice, so that the vaccine came before symptoms began1.
The vaccinated mice had fewer neurofibrillary tangles, the technical name for tau tangles1. Psychiatric Times summarized the finding as BCG curbing tau tangles by boosting cleanup by microglia, the brain’s resident immune cells1.
Bishai pointed out a difference from earlier BCG work in mice. Studies in mouse models of amyloid-beta, the other protein that clumps in Alzheimer’s, found better memory performance but no change in the amount of brain damage1. In this study, he said, the amount of tau tangles itself went down1.
Why anyone looked at a TB vaccine for dementia
BCG has a long record beyond tuberculosis. Bishai said it was used as an immune treatment for many cancers before its effect against bladder cancer was defined in 1975, and it has also been tried against multiple sclerosis, type 1 diabetes and as protection against upper respiratory infections1.
The dementia link comes mainly from looking back at medical records. Retrospective studies of people with bladder cancer, who are often treated with BCG, have linked the treatment with fewer later cases of dementia1. Bishai said these studies show statistically significant benefits in people who got BCG compared with those who did not, and that some small forward-looking trials found a beneficial effect on dementia biomarkers, which are measurable signs in the body linked to the disease1.
Bishai said his interest grew after a symposium marking the 100th anniversary of BCG at the Institut Pasteur in Lille, France, where Calmette and Guérin did their original work1. He recounted a story told there about an elderly scientist who grows BCG in the lab and drinks it, believing it protects against dementia1. That is one person’s practice, not evidence, and nothing in the study tested it.
How the immune system may come into it
Scientists have many theories about what drives Alzheimer’s. Bishai listed faulty handling of amyloid and tau proteins, problems with fat transport in the brain, trouble in the cell’s recycling system, failing mitochondria (the cell’s power plants), blood vessel disease and even infections1. A misfiring immune system is another proposed cause, which could slow protein cleanup, damage connections between nerve cells and feed rising inflammation1.
Microglia are central to that idea. They help clear clumps of amyloid-beta and tau, but when they become overactive, a state called microgliosis, they are also a known feature of Alzheimer’s and a source of lasting inflammation1. Because BCG strongly stimulates the immune system, Bishai said the new work supports the idea that adjusting the immune system might prevent Alzheimer’s-related damage to the brain1.
His personal view is that BCG’s effect works through “trained immunity,” in which immune cells are reprogrammed in lasting ways that change how they behave1. He presented that as his opinion, not a measured result.
What the study does not show yet
- It is in mice. PS19 mice are bred to develop tau disease. Human Alzheimer’s develops over decades and involves more than tau, so results in these animals may not carry over.
- It tested prevention, not treatment. The mice got the vaccine before symptoms. Bishai said experiments are under way to see whether BCG helps after symptoms start1.
- The human data cannot prove cause. The bladder cancer findings come from looking back at records, which can show a link but not that the vaccine itself lowered dementia risk1.
- Key details are not in the sources. The sources available to Biohack do not give the number of mice, the size of the drop in tangles, whether memory or behavior was tested in these mice, the journal or the funding.
Who is behind it
Bishai said his career has focused on tuberculosis, including work to build modified BCG strains that might work better against tuberculosis and as bladder cancer treatment1. He co-wrote the Psychiatric Times article that presents the interview1. The source does not list who paid for the study or whether any company is involved.
Bishai also noted a practical point. Other vaccines have been linked with dementia prevention, but BCG is not used in the United States or western Europe, so if it proves effective it could add protection beyond what people already get from existing vaccines1.
How it fits the field
The idea of a vaccine against dementia is not new, and mouse results have raised hopes before. In early 2020, researchers in the United States and Australia reported that an experimental vaccine aimed directly at amyloid-beta and tau worked in mice with both kinds of damage, and one scientist suggested human trials could start within about two years2. That approach trains the body to make antibodies against the proteins themselves, which is different from BCG’s broad immune boost2. The same report noted that several promising drug candidates had failed in clinical trials2.
Interest in microglia is also growing. In February 2026, the Glenn Biggs Institute at UT Health San Antonio received a two-year, $402,500 grant from the Cure Alzheimer’s Fund for research led by Sarah C. Hopp on how microglia affect the spread of the disease3. Her earlier work suggests microglia, which normally clear waste and damaged proteins, may sometimes help spread toxic tau by accident3. That work aims to find how to keep microglia in a “protective mode”3. Together, these lines of research show the same immune cells may help or harm depending on their state, which is one reason results like BCG’s need careful testing.
What to watch next
- Results from the ongoing mouse experiments giving BCG after symptoms appear1.
- Follow-up work using the PS19 mouse results to work out how BCG acts in the brain, which Bishai said could also shed light on what drives dementia1.
- Any registered human trial testing BCG for dementia prevention, which Bishai said faces no real obstacles given the vaccine’s safety record1.
Biohack will follow this thread as new results are published.
