BCG vaccine may be a weapon against Alzheimer’s disease – GWC Mag

New research shows that the 100-year-old BCG vaccine for tuberculosis may reduce the risk of developing Alzheimer’s disease. I don’t want to call it a “miracle vaccine,” but it’s used to treat bladder cancer, and research is underway to use the BCG vaccine to reverse type 1 diabetes, treat liver cancer, and treat or prevent other diseases that are too many to list.

There are reasons why the BCG vaccine has such a broad usage, and it’s more than just preventing tuberculosis, for which the vaccine was originally developed.

Let’s take a look at the research into how the BCG vaccine may help prevent Alzheimer’s disease.

What is the BCG vaccine?

The Bacillus Calmette-Guérin vaccine, or BCG vaccine, was initially developed to prevent tuberculosis. That disease is caused by a bacteria called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but they can also damage other parts of the body. Tuberculosis is treatable with advanced medicines, but it takes a long time and can be expensive. Without treatment, the patient will die.

The BCG vaccine works like most vaccines – it is made from a live attenuated bovine tuberculosis bacillus, Mycobacterium bovis which induces an adaptive immune response against tuberculosis bacterium.

Tuberculosis (TB) is a leading cause of infectious disease deaths worldwide, second only to COVID. The vaccine’s development began in Lille, France in 1900, when Albert Calmette, an army physician, was working with Camille Guérin, a veterinarian, to understand how TB was transmitted.

Calmette and Guérin cultured TB bacteria on potato slices and found that after several passages of the microbes from one slice to a fresh one, they became less virulent over time. The researchers started to vaccinate calves with this live, weakened form of TB to protect cattle. By 1921, after over 200 generations of this weakened bacteria, the TB strain was stable and did not cause the disease in all animals they tested it on.

At the time of the vaccine’s development, French children born in a family in which someone had TB faced a 25 percent chance of dying from the disease within their first year of life. In 1921, Calmette and Guérin gave the first dose of BCG to a child born into a family with TB, and the child survived.

In 1924, a large clinical trial of more than 5,000 French children showed that the BCG vaccine had 93% effectiveness in preventing death in the first year of life. Based on the results of the clinical trial, France quickly adopted the vaccine, and soon thereafter, many more countries developed their version of the BCG vaccine and began mass vaccination of children.

As a result of the vaccine, tuberculosis was successfully eradicated in many countries, and the vaccine is rarely used in those countries. However, it continues to be given to about 100 million children every year in countries where tuberculosis is still endemic.

Besides protecting people from TB, it seems to reduce the risk of many other infections because of its nonspecific effects on the immune system. In a recent clinical trial, BCG vaccinations halved the odds of developing a respiratory infection over the following 12 months, compared with the people receiving a placebo. This is more data that the BCG vaccine has some effect on the immune system beyond just preventing tuberculosis.

The BCG vaccine works like all vaccines in that it induces an adaptive immune response that “remembers” the pathogen, in this case, the tuberculosis bacteria. However, when used as a cancer “vaccine,” it promotes an immune response that helps destroy the cancer, but it is not preventative, it is an adjuvant therapy called immunotherapy which is used along with chemotherapy, surgery, and radiation, as a part of the cancer treatment strategy.

In the case of Alzheimer’s disease, the BCG vaccine prevents the disease because of these “nonspecific” effects of the vaccine.

What is Alzheimer’s disease?

Before proceeding, it’s important to describe what we know about Alzheimer’s disease (AD). It is a chronic neurodegenerative disease that usually starts slowly and worsens over time. It accounts for 60-70% of dementia cases, even though the terms are sometimes used interchangeably. Alzheimer’s disease is a form of dementia. The other forms of dementia include Lewy body dementia, frontotemporal disorders, vascular dementia, and mixed dementia, which is a combination of two or more of the different forms of dementia.

Amyloid plaques (caused by amyloid beta, or Aβ), phosphorylated tau tangles (pTau), and neurofibrillary tangles are generally easily visible pathologies that can be observed by microscopic analysis of brain tissue from autopsies of those potentially afflicted by AD. These plaques and tangles seem to affect nerve functioning. Despite these observations, the precise pathophysiology, or development, of the disease is not known.

Since amyloid plaques are often identified in patients with Alzheimer’s disease, a large amount of research is focused on attacking those plaques as a way to reverse the effect on nerves which leads to AD.

The causes of AD are unknown (notice how much we do not know about this disease). However, it is speculated that it is mostly genetically related, with a large number of genes that underlie this relationship.

And since we have no clear understanding of the etiology and pathophysiology of AD, there are no effective treatments available today for the disease, although there are some drugs that target the amyloid plaques but have not been shown to change the course or outcomes of AD.

There are a couple of medications that help manage some of the symptoms of the disease, but they are certainly not cures. There are several drugs at the very earliest stages of development that may hold out hope to treat the underlying disease.

One more thing that needs to be made clear. There are no biological tests for Alzheimer’s disease — usually, you can only find the amyloid plaques and other pathologies in post-mortem autopsies. Unfortunately. in the absence of an autopsy, clinical diagnoses of AD are “possible” or “probable”, based on other findings, such as memory tests and other methods.

In the United States, about 10.7% of seniors (≥65 years) currently have Alzheimer’s dementia, and the incidence of dementia and Alzheimer’s disease is expected to rise substantially in the coming decades due to population aging, making it imperative to identify modifiable risk factors that may help mitigate its impact. The economic burden of AD is expected to surpass $2.8 trillion by 2030.

Research on the BCG vaccine and Alzheimer’s disease

The best study that examined the effect of the BCG vaccine on Alzheimer’s disease was published on 1 May 2023 in the respected JAMA Network Open. Marc S. Weinberg, MD, Ph.D., Department of Psychiatry, Massachusetts General Hospital, Charleston, Massachusetts, and colleagues examined 6467 patients who had non-muscle-invasive bladder cancer and who received typical treatment that included the BCG vaccine.

The authors believed that the nonspecific effects arise from a process called “trained immunity.” After a person receives the BCG vaccine, the body increases the production of cytokines, which are small molecules that “kick-start” the immune system into action.

This causes the immune system to respond more efficiently to a threat, such as a virus, bacteria, or cancer cell.

This immune system response could help keep pathogens out of the brain, reducing the risk of Alzheimer’s disease or dementia. Moreover, it may signal the immune system to clean out the amyloid beta proteins that have been correlated to Alzheimer’s disease.

Here are the key findings from their research:

• Treatment of bladder cancer with BCG vaccine lowered the risk of Alzheimer’s disease and dementia by 20%.
• In patients 70 years or older, the reduction was 26%.

It did not eliminate the risk of Alzheimer’s disease, but it was a statistically significant reduction. Furthermore, the BCG vaccine was given as a treatment for bladder cancer — scientists need to research how the vaccine should be given to lower the risk of Alzheimer’s disease even more.

Summary

There is much more evidence that the BCG vaccine can greatly lower the risk of Alzheimer’s. A meta-analysis published in August 2023 showed that there was an average risk reduction of 45% across five studies. That’s a statistically large risk reduction that might make some of us run down to our doctor’s office to get the BCG vaccine.

A 2019 study in Israel that also looked at the difference in risk between individuals who received the BCG vaccine for the treatment of bladder cancer compared to those who didn’t found a 73.1% reduction in risk for Alzheimer’s disease. That difference could be considered “amazing.”

To be completely scientific, we don’t have any results from a large, formal study that compares the risk of Alzheimer’s disease between vaccinated and unvaccinated groups. That will be convincing.

But, there is something here — the BCG vaccine might reduce the risk of Alzheimer’s disease. I hope that this research inspires large clinical trials or cohort studies that lead to a public health effort to begin providing the vaccine to people as they get older. It could help defeat one of the diseases that afflict aging people.

Citations

• Giamarellos-Bourboulis EJ, Tsilika M, Moorlag S, Antonakos N, Kotsaki A, Domínguez-Andrés J, Kyriazopoulou E, Gkavogianni T, Adami ME, Damoraki G, Koufargyris P, Karageorgos A, Bolanou A, Koenen H, van Crevel R, Droggiti DI, Renieris G, Papadopoulos A, Netea MG. Activate: Randomized Clinical Trial of BCG Vaccination against Infection in the Elderly. Cell. 2020 Oct 15;183(2):315-323.e9. doi: 10.1016/j.cell.2020.08.051. Epub 2020 Sep 1. PMID: 32941801; PMCID: PMC7462457.
• Gofrit ON, Klein BY, Cohen IR, Ben-Hur T, Greenblatt CL, Bercovier H. Bacillus Calmette-Guérin (BCG) therapy lowers the incidence of Alzheimer’s disease in bladder cancer patients. PLoS One. 2019 Nov 7;14(11):e0224433. doi: 10.1371/journal.pone.0224433. PMID: 31697701; PMCID: PMC6837488.
• Han C, Wang J, Chen YL, Guan CP, Zhang YA, Wang MS. The role of Bacillus Calmette-Guérin administration on the risk of dementia in bladder cancer patients: a systematic review and meta-analysis. Front Aging Neurosci. 2023 Aug 24;15:1243588. doi: 10.3389/fnagi.2023.1243588. PMID: 37693645; PMCID: PMC10484104.
• Trunk G, Davidović M, Bohlius J. Non-Specific Effects of Bacillus Calmette-Guérin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Vaccines (Basel). 2023 Jan 4;11(1):121. doi: 10.3390/vaccines11010121. PMID: 36679966; PMCID: PMC9866113.
• Weinberg MS, Zafar A, Magdamo C, Chung SY, Chou WH, Nayan M, Deodhar M, Frendl DM, Feldman AS, Faustman DL, Arnold SE, Vakulenko-Lagun B, Das S. Association of BCG Vaccine Treatment With Death and Dementia in Patients With Non-Muscle-Invasive Bladder Cancer. JAMA Netw Open. 2023 May 1;6(5):e2314336. doi: 10.1001/jamanetworkopen.2023.14336. PMID: 37204792; PMCID: PMC10199345.