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Q&A #70 with Dr. Rhonda Patrick (5/3/25)

Posted on May 15th 2025 (about 1 month)

Dr. Rhonda Patrick discusses cancer prevention, linoleic acid, shingles vaccine and dementia, creatine's kidney effects, and shares her overnight oats recipe.

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Q&A #64 with Dr. Rhonda Patrick (11/2/24)

Posted on November 19th 2024 (7 months)

Dr. Rhonda Patrick discusses silicone safety, grounding, pentadecanoic acid, and the potential benefits of olive leaf extract and peptides.

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Q&A #42 with Dr. Rhonda Patrick (12/3/22)

Posted on December 3rd 2022 (over 2 years)

Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.

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News & Publications

  • Experimental vaccine may prevent peanut allergy. newatlas.com
    Immune System Vaccine Allergies

    A recent study demonstrated that an experimental mRNA-based vaccine prevented peanut allergy in mice. The vaccine effectively induced peanut protein tolerance, reducing or preventing symptoms of allergy.

    Researchers developed a lipid nanoparticle vaccine that delivered mRNA-encoded peanut allergen and administered it to mice that are prone to peanut allergy. Then they exposed the mice to peanut protein and assessed their immune response.

    They found that the mRNA vaccine induced the production of T regulatory cells, a specialized type of T cells that suppress the body’s immune response. The vaccine also reduced cytokine production, antibody synthesis, and mast cell release – indicators of an allergic response.

    Peanut allergy is one of the most common food allergies, affecting approximately 2 percent of adults and children in the United States. Typically manifesting early in life, symptoms of peanut allergy include rashes, shortness of breath, and life-threatening anaphylaxis.

    mRNA-based vaccines contain the genetic material to encode a single protein that, when injected into the body, induces antibody production against that protein – in this case, a peanut allergen. Because mRNA degrades easily, it must be encapsulated in lipid nanoparticles.

    These findings suggest that an mRNA-based vaccine prevents peanut allergy in mice. Although mRNA-based vaccines have been used in clinical trials for nearly two decades, this study reflects their first use against an allergen. Learn more about mRNA vaccines in this clip featuring Dr. Roger Seheult.

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  • Gene-edited tumor cells used as a "tumor-killing" cancer vaccine in a new approach to treating glioblastoma. medicalxpress.com
    Cancer Immune System Vaccine

    An experimental vaccine killed brain cancer cells and prevented them from returning, a new study in mice has found. The mice lived longer and had improved anti-cancer immunity.

    Using CRISPR-Cas9, a powerful gene editing tool, researchers modified living tumor cells so that they would secrete interferon-beta and granulocyte-macrophage colony-stimulating factor – two potent immunomodulatory and anti-tumor agents. Then they incorporated a “kill switch” in the modified cells that would prevent secondary tumor initiation.

    They found that the modified tumor cells killed glioblastoma tumor cells by inducing apoptosis (cell death) and turning off the activity of cancer growth factors. The modified cells also turned on normal anti-cancer immune cell activities and signaling, improving the animals' survival and promoting their long-term immunity.

    This study in mice provides proof of concept for the use of genetically modified living tumor cells as anti-tumor agents and paves the way for their future use in humans. Learn more about therapeutic uses of gene editing in this episode featuring Dr. George Church.

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  • High testosterone may indirectly weaken immune response to vaccination in men by interacting with related genes. (2013) www.sciencedaily.com
    Hormones Immune System Vaccine Testosterone

    From the article:

    In the study, women had a generally stronger antibody response to the vaccine than men. But the average response mounted by men with relatively low testosterone levels was more or less equivalent to that of women.

    […]

    Women are known to have, on average, higher blood levels of signaling proteins that immune cells pass back and fort to jump-start inflammation, a key component of immune-system activation. Furthermore, previous research in animals and in cell-culture experiments has established that testosterone has anti-inflammatory properties, suggesting a possible interaction between the male sex hormone and immune response.

    […]

    However, the new study found no connection between circulating levels of pro-inflammatory proteins and responsiveness to the flu vaccine. Nor does testosterone appear to directly chill immune response; rather, it seems to interact with a set of genes in a way that damps that response, said the study’s senior author, Mark Davis, PhD, professor of microbiology and immunology and director of Stanford’s Institute for Immunity, Transplantation and Infection.

    […]

    Men are prone to suffer wounds from their competitive encounters, not to mention from their traditional roles in hunting, defending kin and hauling things around, increasing their infection risk.

    While it’s good to have a decent immune response to pathogens, an overreaction to them – as occurs in highly virulent influenza strains, SARS, dengue and many other diseases – can be more damaging than the pathogen itself. Women, with their robust immune responses, are twice as susceptible as men to death from the systemic inflammatory overdrive called sepsis. So perhaps, Davis suggests, having a somewhat weakened (but not too weak) immune system can prove more lifesaving than life-threatening for a dominant male in the prime of life.

    View full publication

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  • Getting a flu shot reduced the development Alzheimer's by 40 percent. medicalxpress.com
    Alzheimer's Vaccine

    Background: Prior studies have found a reduced risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions. However, the effect of influenza vaccination on Alzheimer’s disease (AD) risk in a general cohort of older US adults has not been characterized.

    Objective: To compare the risk of incident AD between patients with and without prior influenza vaccination in a large US claims database.

    Methods: Deidentified claims data spanning September 1, 2009 through August 31, 2019 were used. Eligible patients were free of dementia during the 6-year look-back period and≥65 years old by the start of follow-up. Propensity-score matching (PSM) was used to create flu-vaccinated and flu-unvaccinated cohorts with similar baseline demographics, medication usage, and comorbidities. Relative risk (RR) and absolute risk reduction (ARR) were estimated to assess the effect of influenza vaccination on AD risk during the 4-year follow-up.

    Results: From the unmatched sample of eligible patients (n = 2,356,479), PSM produced a sample of 935,887 flu–vaccinated-unvaccinated matched pairs. The matched sample was 73.7 (SD, 8.7) years of age and 56.9% female, with median follow-up of 46 (IQR, 29–48) months; 5.1% (n = 47,889) of the flu-vaccinated patients and 8.5% (n = 79,630) of the flu-unvaccinated patients developed AD during follow-up. The RR was 0.60 (95% CI, 0.59–0.61) and ARR was 0.034 (95% CI, 0.033–0.035), corresponding to a number needed to treat of 29.4.

    Conclusion: This study demonstrates that influenza vaccination is associated with reduced AD risk in a nationwide sample of US adults aged 65 and older.

    https://content.iospress.com/articles/journal-of-alzheimers-disease/jad220361

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  • Novel amyloid-beta vaccine reduces Alzheimer’s-like dementia in mice. www.sciencedaily.com
    Alzheimer's Vaccine

    Alzheimer’s disease is a neurodegenerative disease characterized by aggregates of misfolded proteins such as amyloid-beta and tau in the brain. Previous research has attempted to use amyloid-beta vaccines to stall or reverse the progression of Alzherimer’s disease; however, these trials failed to produce a vaccine that was effective and safe00023-6/fulltext). A study released this week has identified a new target for Alzheimer’s disease vaccines that may succeed in clearing amyloid-beta plaques.

    Amyloid-beta is a small, 36-43 amino acid protein that is cleaved from a larger amyloid precursor protein in the brain. After being cleaved, the small amyloid-beta protein can become misfolded, lose its function, and form oligomers, which are aggregate protein structures with many repeating identical units. Some of the amino acids on one end of the amyloid-beta structure fold over, creating a hairpin structure and contributing to plaque formation. Previous research has suggested the hairpin site is an effective target for preventing aggregation; however, no vaccine has yet been developed that exploits this molecular pattern.

    The authors designed a peptide that is a portion of the amyloid-beta protein containing 14 amino acids that are cyclized to form a stable pseudo hairpin structure. They inoculated healthy mice with the cyclized peptide and measured the antibody response. Next, they immunized mice who exhibit Alzheimer’s-like dementia and measured the effect on amyloid-beta plaques in the brain. They also measured cognitive function and hippocampal volume, which both decline with Alzherimer’s disease.

    The authors found that healthy mice had a robust immune response to immunization and produced antibodies specific to the pseudo hairpin protein they designed. In mice who develop Alheimer’s-like dementia, immunization significantly reduced the amount of amyloid-beta plaques in regions of the brain such as the cerebral cortex, hippocampus, and thalamus. These regions also exhibited increased glucose metabolism following immunization, indicating better metabolic health in the brain. Finally, immunization increased the number of neurons in the hippocampus, the brain region most associated with learning memory. Immunized mice with greater hippocampal volume performed better on learning and memory tasks.

    Immunization with the novel pseudo hairpin structure reversed amyloid-beta aggregation in the brain and improved brain health and cognitive performance in mice. This exciting research may contribute to the development of Alzheimer’s disease vaccines in humans.

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  • mRNA vaccines provide long-lasting immunity and protection from SARS-CoV-2 variants. www.bloomberg.com
    Immune System Vaccine COVID-19

    SARS-CoV-2 mRNA vaccines (e.g., Moderna and Pfizer-N-BioTech) are effective in preventing infection and have even greater efficacy in preventing severe COVID-19 illness and hospitalization. However, many people in the United States received their vaccine early in 2021, more than six months before the time of this writing. Whether the protection afforded by vaccination lasts as time passes and more SARS-CoV-2 variants emerge is unclear. Findings of a report published in August provide insights into long-term immunity following vaccination or SARS-CoV-2 infection, concerns about emerging variants, and implications for vaccination boosters.

    During infection with a virus, the innate immune system immediately produces inflammation to fight the infection. Within days or weeks, the adaptive immune system produces antibodies that are specific to the virus. These antibodies bind to a small piece of the viral particle, called an antigen. White blood cells such as macrophages and neutrophils participate in the innate response, while B and T cells facilitate the adaptive response. Plasma B cells are responsible for producing antibodies; however, these cells steadily decrease in number over time. Memory B cells store the genetic information needed to produce virus-specific antibodies upon reinfection. Memory T cells are also responsible for “remembering” viruses in this way. Memory CD4+ T cells rapidly respond to reinfection to support inflammation and antibody production. Memory CD8+ T cells, also called cytotoxic T cells, bind to virus-infected host cells and order them to undergo apoptosis (i.e., programmed cell death).

    The authors of the report analyzed a set of 342 blood samples collected from 61 participants at one, three, and six months following vaccination. This group of participants included SARS-CoV-2 naive individuals (i.e., those who were never infected with the virus) and SARS-CoV-2 recovered individuals. The investigators measured the concentration of circulating antibodies that bind to the SARS-CoV-2 receptor binding domain protein and spike protein. They also measured the concentration of memory B cells and T cells and characterized these cells’ response when challenged with SARS-CoV-2 antigens.

    The concentration of serum antibodies declined over time, but was still detectable at six months post-vaccination. mRNA vaccination produced memory B cells that respond to the receptor binding domain protein of the Alpha, Beta, and Delta variants, called cross-binding memory. These memory B cells had significantly more hypermutation, the process by which B cells rearrange their DNA in order to produce antibodies to new antigens, and increased in concentration between three and six months post-vaccination. Cross-binding B cells were more common in SARS-CoV-2 recovered patients than naive patients. mRNA vaccination also increased memory CD4+ and CD8+ T cells.

    The immune response to mRNA vaccination and infection with the SARS-CoV-2 virus evolves over time, which may have implications for the future use of booster vaccines. These results should be considered with caution as this research has yet to be peer-reviewed.

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  • Low antibody levels in vaccinated people predict risk of breakthrough infection. www.nature.com
    Vaccine COVID-19

    Messenger RNA (mRNA) vaccines, such as the Pfizer and Moderna vaccines, have significantly reduced SARS-CoV-2 infection and COVID-19 disease rates in areas with vaccine availability. However, a small number of people who have received both doses of an mRNA vaccine have reported breakthrough cases with mild COVID-19 symptoms. New findings suggest people with breakthrough SARS-CoV-2 infection have lower than normal antibody levels preceding infection.

    Recent research has reported breakthrough cases of COVID-19 in just four percent of nursing home residents and staff in Chicago, while a report from Kentucky found breakthrough infections in 25 percent of fully vaccinated residents and seven percent of fully vaccinated staff. A study of healthcare workers who had received an mRNA vaccine in India found breakthrough infections in 13 percent of participants. In all studies, symptoms experienced by those with a breakthrough infection were significantly milder and were less likely to require hospitalization than in unvaccinated people. So far, no predictor of breakthrough infection has been identified.

    The investigators performed their research at Israel’s largest medical center where 91 percent of staff received two doses of a SARS-CoV-2 mRNA vaccine in January 2021. Workers underwent testing for infection using an RT-PCR assay, which measures the amount of viral RNA in a sample. During the same month, Israel experienced a surge in COVID-19 cases, providing good conditions for detecting nearly all breakthrough infections in this population. A breakthrough infection was defined as the detection of SARS-CoV-2 using an RT-PCR assay performed 11 or more days after the second dose of vaccine if no direct exposure or symptoms were reported during the first six days following the second vaccine dose. For each participant who had a breakthrough infection, the researchers found four to five uninfected staff members and compared antibody levels among them.

    Among the nearly 1,500 participants who had available RT-PCR data, only 39 participants (three percent) experienced a breakthrough case. Participants with breakthrough infections had lower antibody levels in the week preceding the onset of symptoms than uninfected vaccinated participants. As the concentration of neutralizing antibodies increased, the risk of breakthrough infection decreased. Most breakthrough cases resulted in mild symptoms such as upper respiratory congestion, muscle aches, fever, and loss of taste and smell. While most symptoms resolved after six weeks, 19 percent of breakthrough cases were “long COVID-19” cases with prolonged symptoms. In all breakthrough cases, contact with an unvaccinated person was the suspected exposure.

    This research suggests that testing of antibody levels following vaccination may identify individuals susceptible to breakthrough infection. Previous infection with the SARS-CoV-2 virus provides additional protection, called hybrid immunity. A report covered in this edition of the Science Digest found that people with hybrid immunity are more protected from reinfection with variant strains.

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  • COVID-19 vaccines are less effective against the delta variant, especially the Pfizer-BioNTech vaccine. www.axios.com
    Vaccine COVID-19

    As the COVID-19 pandemic continues into its second year, a number of variants have emerged, such as the delta variant, which is a highly contagious SARS-CoV-2 variant first identified in India in December 2020. The increase in transmissibility - the ability of a disease to be passed from one individual to another - is due to mutations of the viral spike protein, which allows entry into human cells. Findings of a report released this week show that vaccines that were effective against the original SARS-CoV-2 strain are less effective against the delta variant.

    Viruses are small particles containing genetic material (RNA in the case of SARS-CoV-2) and a lipid capsule with protein structures on the surface. They do not contain the cellular machinery to create new viruses and depend on host cells for replication. Messenger RNA (mRNA) vaccines, such as the Pfizer-BioNTech and Moderna vaccines, work by delivering modified viral RNA encapsulated in a lipid membrane to human cells. These lipid droplets fuse with the lipid membranes of human cells in the respiratory tract and elsewhere and deliver mRNA to the inside of the cell. Once inside the cell, the vaccine mRNA directs the cell to produce more of the modified viral protein. This tricks the immune system into thinking these cells are infected and the body mounts an immune response that ultimately results in the production of antibodies that bind to the SARS-CoV-2 spike protein, preventing subsequent infection.

    Reports published before the emergence of the delta variant demonstrate an efficacy of 95 percent for the Pfizer-BioNTech vaccine and 93 percent for the Moderna vaccine against the original Wuhan Hu-1 strain. Because the delta variant has a modified spike protein, it is unclear if vaccines designed for the original SARS-CoV-2 spike protein will be effective against current and future variants.

    The authors analyzed data from patients of the Mayo Clinical Health System in Minnesota, Wisconsin, Arizona, Florida, and Iowa starting in January 2021, when the original SARS-CoV-2 strain was most prevalent, and ending in July 2021, when the delta variant was most prevalent. The study included more than 25,000 vaccinated participants and 25,000 unvaccinated participants matched for age, sex, race, ethnicity, state of residence, and history of prior SARS-CoV-2 testing.

    The delta variant prevalence in Minnesota increased from less than one percent in May 2021 to over 70 percent in July 2021; whereas the original strain prevalence decreased from 85 percent to 13 over the same period. The researchers found that the Moderna vaccine was between 81 and 91 percent effective and the Pfizer-BioNTech vaccine was between 69 and 81 percent effective against infection with the original SARS-CoV-2 virus prior to May 2021. These vaccines were also highly effective in preventing hospitalization from infection with the original virus with the Moderna vaccine showing 81 to 97 percent efficacy and the Pfizer-BioNTech vaccine showing 73 to 93 percent efficacy. By July, the total effectiveness in preventing infection decreased to 76 percent for the Moderna vaccine and 42 percent for the Pfizer-BioNTech vaccine, indicating a loss of efficacy over time as variants became more common.

    Next, the authors compared vaccine effectiveness across multiple states over the entire study period. In most states, the Moderna vaccine was twice as effective in preventing breakthrough infections than the Pfizer-BioNTech vaccine. This difference in effectiveness against breakthrough infections between the vaccines was highest in July, when the delta variant was most prevalent. This was especially true in Florida, where the risk of breakthrough infection was 60 percent lower after vaccination with the Moderna vaccine compared to the Pfizer-BioNTech vaccine. Across all dates, the Moderna vaccine was twice as effective in preventing COVID-19 associated hospitalization compared to the Pfizer-BioNTech vaccine.

    While both vaccines demonstrate effectiveness in preventing infection and hospitalization, their effectiveness has declined over time as the prevalence of SARS-CoV-2 variants increased. The authors suggested additional studies in large and diverse populations are needed to guide public health policy. This manuscript has yet to be peer-reviewed.

    Previous infection with the original strain of the SARS-CoV-2 along with vaccination creates what is known as “hybrid immunity.” People who have hybrid immunity have a broader and more robust antibody response, as observed in this trial, which is covered in this edition of the Science Digest.

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  • Previous infection with SARS-CoV-2 plus vaccination protects against variants. www.nature.com
    Vaccine COVID-19

    The delta variant of SARS-CoV-2, the virus that causes COVID-19, is one of multiple variants to exhibit increased resistance to antibodies as well as higher transmissibility. It is unclear if vaccination or prior infection with the original Wuhan Hu-1 strain is effective against these emerging variants. But now, a new report suggests individuals who have recovered from infection with the original SARS-CoV-2 strain are protected from variants such as delta, especially following vaccination.

    A virus strain is considered the “parent” form of a virus. For example, SARS-CoV-1 and SARS-CoV-2 are strains of the broader SARS-CoV line of viruses. To be considered a variant, a virus must have sufficient mutations to change a portion of its genetic code. In the case of the delta variant, increased transmissibility is the result of genetic changes to the receptor binding domain, a portion of the viral spike protein. This protein enables viruses to enter cells and is the main target of SARS-CoV-2 vaccines. Its genetic change in the delta variant has scientists concerned that individuals who have recovered from the original virus or an early variant may not be protected against later variants with altered spike proteins.

    During infection with a virus, the innate immune system immediately produces inflammation to fight the infection. Within days or weeks, the adaptive immune system produces antibodies that are specific to the virus. These antibodies bind to a small piece of the viral particle, called an antigen. Plasma B cells are the white blood cells responsible for producing antibodies; however, these cells steadily decrease in number over time and do not protect against reinfection with the same virus. Memory B cells store the genetic information needed to produce virus-specific antibodies upon reinfection.

    The authors of the novel report recruited 63 participants between the ages of 26 and 73 years old who were convalescent, meaning they had recovered from SARS-CoV-2 infection. Some participants had received a vaccine (only mRNA vaccines were included) and others had not. The researchers collected blood samples from their participants at about six weeks, six months, and one year following infection in order to characterize their immune responses specifically to the receptor binding domain of the SARS-CoV-2 spike protein. Immunity measures included specificity (the number of antigens to which an antibody will bind), reactivity (the strength to which an antibody binds its antigen), and neutralizing activity (the antibodies' ability to block infection).

    Their analysis revealed that convalescent participants who had not been vaccinated maintained their plasma antibody levels 12 months following infection, providing protection from reinfection. Notably, convalescent participants who had received an mRNA vaccine had 30 times more antibodies and 50 times greater neutralizing activity against the original SARS-CoV-2 strain 12 months following infection than unvaccinated convalescent participants. Neutralizing activity against the alpha, beta, iota, and gamma variants was also ten times greater at 12 months compared to vaccinated individuals who have never had the virus. This means the immune system will react strongly if a vaccinated convalescent individual catches one of the viral variants.

    Antibody-producing B cells evolved over time in both vaccinated and unvaccinated convalescent participants; however, receiving an mRNA vaccine increased receptor binding domain antibodies eightfold. Without vaccination, convalescent participants lost a significant portion of antibodies that were specific for the receptor binding domain of the spike protein at six months post-infection, putting them at greater risk for reinfection. The authors showed that memory B cells continually mutate their antibody structures to increase reactivity and specificity over time, providing stronger immunity against a wider array of strains.

    The authors concluded that immunity in convalescent individuals is long lasting. Vaccination provides additional protection against SARS-CoV-2 variants in convalescent individuals. However, an article covered in this edition of the Science Digest suggests current mRNA vaccines may be less effective against the delta variant in vaccinated people who have never had a SARS-CoV-2 infection.

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  • A multi-state mumps outbreak among fully vaccinated people in the United States. www.scientificamerican.com
    Vaccine

    Mumps is a highly contagious viral infection characterized by swelling of the salivary glands and accompanied by fever, fatigue, body aches, and appetite loss. Severe complications of the disease include pancreatitis and encephalitis. A recent report from the Centers for Disease Control and Prevention (CDC) describes a recent, ongoing outbreak of mumps in the United States.

    Commonly referred to as a “childhood disease,” mumps affects people of all ages, but it is largely preventable by vaccination. The vaccine is delivered in two doses, typically over a period of a few years, in combination with vaccines against measles and rubella. A single dose of the vaccine reduces the risk of mumps infection by 78 percent; two doses reduce risk by 88 percent.

    The outbreak began in August 2019 when 30 people who attended a wedding in Nebraska later developed the disease. The index patient was not only asymptomatic but was also fully vaccinated. Eventually, 62 patients (41 of whom were fully vaccinated) were diagnosed with mumps related to the index case.

    Vaccines are the cornerstone of public health programs to prevent disease and death. Unfortunately, vaccination rates for children have dropped due to the ongoing COVID-19 pandemic. A mumps outbreak in a highly vaccinated population emphasizes the importance of vaccination to prevent spread to unvaccinated people but also raises questions about presumed lifelong immunity from childhood vaccines.

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  • Successful MERS vaccine in mice may hold promise for COVID-19 vaccine www.eurekalert.org
    Vaccine COVID-19

    From the article:

    “The vaccine is an innocuous parainfluenza virus (PIV5) carrying the "spike” protein that MERS uses to infect cells. All the vaccinated mice survived a lethal dose of the MERS coronavirus. […] The researchers note several factors that make PIV5 expressing a coronavirus spike protein an appealing platform for vaccine development against emerging coronaviruses. First, PIV5 can infect many different mammals, including humans, without causing disease. PIV5 is also being investigated as a vaccine for other respiratory diseases including respiratory syncytial virus (RSV) and influenza. Second, the fact that a low dose of the vaccine was sufficient to protect the mice might be beneficial for creating enough vaccine for mass immunization. And finally, the vaccine in the current study was the most effective MERS vaccine to date in animal models of the disease."

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  • A vaccine developed to prevent tuberculosis, now also used to treat bladder cancer, reduced the incidence of Alzheimer’s disease four-fold. journals.plos.org
    Alzheimer's Vaccine

    Alzheimer’s disease is a neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. It is the most common form of dementia, affecting nearly 50 million people worldwide. Findings from a recent study suggest that the bacillus Calmette-Guérin vaccine, originally developed to provide immunity against tuberculosis and now widely used to treat bladder cancer, may be useful in reducing the incidence of Alzheimer’s disease in bladder cancer patients.

    A critical element of Alzheimer’s disease pathogenesis is neuroinflammation. Previous research has shown that BCG vaccination triggers an immune response that increases systemic IL-2 levels which, in turn, increases the population of neuroprotective T-reg cells. BCG also increases anti-inflammatory cytokines in the brain, thereby reducing neuroinflammation.

    The new study involved 1,371 patients (average age, 68 years) with bladder cancer who received various agents as intravesical chemotherapy. Of these patients, 878 received BCG treatment. After a median of eight years of follow-up, those who received the BCG intravesical therapy exhibited a four-fold reduction in the risk of developing Alzheimer’s disease. These findings suggest that BCG vaccine treatment might be useful in preventing Alzheimer’s disease.

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