Recent studies suggest that the shingles vaccine and the flu vaccine are associated with a lower risk of developing dementia, including Alzheimer’s. Although neither of these vaccines was developed to address Alzheimer’s, this research suggests that these vaccines and the changes they cause in the immune system have the potential to prevent Alzheimer’s.

This information isn’t new. Scientists have been studying the links between our immune system and Alzheimer’s for decades. Their end goal is to develop a vaccine that can prevent Alzheimer’s.

Many members of myALZteam are eager to learn more about preventive measures. One myALZteam member commented, “I heard about this new ALZ vaccine. What is this all about?” This article will cover all you need to know about the early research on Alzheimer’s vaccines.

The Importance of Vaccines

Vaccination is a powerful method for preventing disease. Vaccination is especially important for diseases that have no treatment.

Currently, some Alzheimer’s symptoms can be treated, but the underlying factors and disease progression cannot. Although health care professionals recommend trying to lower your risk of developing Alzheimer’s by leading a healthy lifestyle, this is no guarantee. As one myALZteam member noted, “My father did everything they say to do … none of it prevented his Alzheimer’s.”

Vaccination has been highly successful at curbing and even ending devastating diseases. Why not Alzheimer’s, too?

Beta-Amyloid: The Target of the First Alzheimer’s Vaccine

Most vaccines today are for infectious diseases caused by viruses or bacteria. The vaccines for these diseases are usually made by introducing a small part of the virus (or bacteria) to the immune system. The cells then recognize this as a target and create cells (called memory cells) to look out for it in the future.

Before a vaccine could be developed for Alzheimer’s, researchers had to identify “targets” for the immune system. In the 1980s, clumps of protein called beta-amyloid plaques were discovered as a cause of Alzheimer’s. These plaques block signals and can kill neurons, which are important brain cells.

The discovery of beta-amyloid plaques meant there was something researchers could target with their vaccine designs. In 1999, researchers used protein to stimulate the immune system. This led to the production of antibodies that targeted beta-amyloids. Antibodies are proteins in our bodies that help remove things that shouldn’t be there. The researchers then showed that the vaccination helped clear beta-amyloid plaques from rodent brains.

The success led to the first clinical trial for an Alzheimer’s vaccine with a vaccine called AN1792. However, these trials were cut short for safety reasons. The same immune response responsible for clearing the plaques also caused severe side effects in some participants. However, the researchers were able to show that the vaccine worked in humans, as it had in mice.

Passive Immunization: The Safer Alternative

The immunization strategy for AN1792 was known as active immunization. The vaccine stimulated the immune system to produce antibodies to attack beta-amyloid plaques. However, this strategy also stimulated other components of the immune system, resulting in severe side effects. After the failure of AN1792, researchers started to study passive immunizations as a safer option for targeting beta-amyloid plaques.

In passive immunizations, individuals are treated directly with antibodies made in a laboratory. Bapineuzumab was the first passive immunization for Alzheimer’s to reach clinical trials. People receiving treatment in these trials did not experience side effects as severe as those seen with active immunization. However, the later-stage clinical trials showed no clear benefits from the vaccine. Bapineuzumab was not studied further.

Trying Another Target: Tau

While studying beta-amyloids, researchers discovered some drawbacks to using them in vaccines. Some parts of the beta-amyloid protein were linked to immune reactions that cause bad side effects. People with the ApoE4 mutation, a genetic mutation (change) that increases the likelihood of developing Alzheimer’s, were especially likely to experience severe side effects. For this reason, researchers started looking into the tau protein as another option for a vaccine target.

The tau protein contributes to Alzheimer’s development by creating “tau tangles." Tau tangles occur when the tau protein causes clumping within neurons. These tangles then block important nutrients from getting to the brain. They can also exacerbate plaques.

Two new vaccines, called AADvac1 and ACI-35, were developed to target tau tangles instead of beta-amyloids. A preliminary study of AADvac1 showed it was safe and caused an immune reaction. However, more clinical studies are needed to confirm that it’s safe and works for prevention. ACI-35 is also in clinical trials.

Breakthroughs With Beta-Amyloid

In recent years, there have been breakthroughs with beta-amyloid vaccines too. By only including the parts of beta-amyloids necessary to trigger an immune response, and by removing the region thought to cause negative side effects, new beta-amyloid active vaccinations have been more successful. CAD106 is one such vaccine currently in clinical trials. It showed improved safety compared to the first vaccine. In CAD106’s first trials, it also showed a reduction in brain plaques. CAD106 will be the first active vaccine for Alzheimer’s to reach phase 2 or phase 3 clinical trials.

In addition to new research into beta-amyloid vaccines, there are therapies available that target beta-amyloid plaques. The first of these drugs to be approved was aducanumab (Aduhelm). This drug was discontinued in May 2024. Two other drugs that aim to remove beta-amyloid plaques are available. These are lecanemab (Leqembi) and donanemab (Kisunla).

New Developing Vaccine Strategies

While improvements to old strategies have yielded more Alzheimer’s vaccines that made it to clinical trials, researchers are also exploring exciting new strategies. Nucleic acid vaccines (vaccines made from DNA or RNA) are one new avenue of research. DNA and RNA contain all of the genetic information in our cells.

Unlike previous vaccines, which were made from proteins, DNA and RNA vaccines contain the instructions that show our bodies how to produce those proteins. The RNA or DNA is delivered to our cells, and then our cells make the protein. For Alzheimer’s vaccines, RNA and DNA vaccines are of interest because they are easy to adjust and probably safer.

The research into DNA and RNA vaccines is still in its early stages. But researchers have shown that DNA vaccines reduced brain plaques in mice without causing any significant side effects. While there are researchers working on RNA vaccines, so far, they have not published any studies.

Finally, researchers are targeting another cause of Alzheimer’s: brain inflammation. Inflammation can be both helpful and harmful for people with Alzheimer’s. It can be helpful by aiding in processes that dissolve and clean up brain plaques. But it can have negative effects, like causing the production of too many beta-amyloids and tau proteins. Vaccines that can help the immune system better dissolve plaques while also preventing problematic inflammation could be highly successful. Bacillus Calmette-Guerin (BCG), a vaccine for tuberculosis, is also used as a vaccine for bladder cancer because it causes helpful inflammation. It’s now in clinical trials as a vaccine for Alzheimer’s.

The Future of Alzheimer’s Vaccines

There are currently many vaccines in clinical trials for Alzheimer's. Additionally, new therapies have recently been approved. That said, the research has shown that once brain damage has occurred, there’s no way to reverse it.

Scientists hope to begin studying these new advances in people that are in the very early stages of Alzheimer’s or have yet to show symptoms. With studies like these, we can better determine if vaccines are able to prevent Alzheimer’s. Vaccines such as CAD106 show the most promise for preventing the disease.

Unfortunately, studies that look at the preventive effects of vaccines will take a long time. People enrolled in the studies will probably have to wait years before knowing if the vaccine worked. For this reason, it will likely be a while before we know if these vaccines truly prevent Alzheimer’s.

Talk With Others Who Understand

On myALZteam, the social network for caregivers of people with Alzheimer's disease, more than 86,000 members come together to ask questions, give advice, and share their stories with others who understand life with Alzheimer’s.

Are you wondering if others with Alzheimer’s have tried these newly approved passive immunizations? Or have you or your loved one tried them yourself? Share your experience in the comments below, or start a conversation by posting on your Activities page.