A preclinical study has tested a new vaccine for Alzheimer’s disease. The researchers found that the vaccine, which targets the beta-amyloid protein, was safe and effective in mice.
Alzheimer’s disease is a progressive neurological condition and the most common cause of dementia.
According to the latest estimates from the Alzheimer’s Association, 1 in 10 people over the age of 65 years in the U.S. have Alzheimer’s disease, and experts expect the number of people with the condition to increase as the population ages. By 2050, projections show that 13.8 million people aged 65 years and over will have Alzheimer’s disease in the U.S.
While groups around the world are working to find an effective treatment for the condition, an alternative approach is to develop a vaccine. Although they are more commonly associated with infectious diseases, vaccines can also prime the body to defend itself against other, noninfectious molecules.
In Alzheimer’s disease, scientists believe that two processes drive the progression of the disease: the buildup of plaques comprising beta-amyloid proteins between neurons in the brain and tangled knots of the tau protein within neurons.
Since the general understanding is that beta-amyloid initiates the disease process, scientists have tried to develop a vaccine against it. The hope is that the immune system recognizes and destroys the beta-amyloid before it can aggravate the cell damage that the tau protein causes.
Although scientists have developed several vaccines, translating the findings from murine models into humans while ensuring safety is notoriously challenging, and the authorities have not yet approved any vaccines for use.
Researchers need to overcome the fact that as people age, their immune system becomes less responsive. As a result, without help, they will have a lower response to a vaccine.
Scientists usually overcome this problem by adding adjuvants that kickstart and enhance the immune response. However, a potential problem is that the adjuvants overstimulate the immune system, leading to inflammation.
A new study that the University of South Florida Health (USF Health) led describes a novel therapeutic vaccine for Alzheimer’s disease, which uses the body’s own immune cells to target beta-amyloid. The study found that this approach avoided the overstimulation of the immune system that can occur due to chemical adjuvants.
The study showed effective antibody production and memory improvements in vaccinated mice, and the findings appear in the Journal of Alzheimer’s Disease.
Harnessing dendritic cells
The new vaccine uses dendritic cells, which communicate with other immune cells, such as B cells and T cells, to guide the immune response.
“This therapeutic vaccine uses the body’s own immune cells to target the toxic [beta-amyloid] molecules that accumulate harmfully in the brain,” explains the senior author of the paper, Dr. Chuanhai Cao.
The dendritic cells are loaded with a modified version of beta-amyloid so that the body can detect and destroy the real thing.
“Because we use dendritic cells to generate antibodies, this vaccine can coordinate both innate and acquired immunity to potentially overcome age-related impairments of the immune system,” adds Dr. Cao.
In the new study, the researchers tested the vaccine in mouse models of Alzheimer’s disease. The mice were genetically modified to produce high levels of beta-amyloid and show cognitive difficulties similar to those that occur in humans with Alzheimer’s disease.
The team gave some of the mice the vaccine, while others received the dendritic cells only (containing no beta-amyloid).
The mice that received the vaccine produced antibodies against beta-amyloid in their brains and blood. They also showed symptom improvements — for example, in memory tests, the vaccinated mice performed similarly to healthy mice.
The vaccinated mice also showed significantly improved working memory compared with mice that received only the dendritic cells. Working memory involves holding and manipulating information for a short time, and deficits in this form of memory are a common feature of Alzheimer’s disease.
Importantly, the vaccine did not cause an inflammatory response in the mice — a major concern when developing a vaccine and the main reason why researchers had to stop using a previous vaccine.
“Inflammation is a primary symptom of Alzheimer’s disease, so any possible treatment with neural inflammation as a side effect essentially pours gas on the fire,” explains Dr. Cao.
This study found no evidence of an inflammatory reaction. There were no significant differences in the amounts of inflammatory molecules called cytokines in the vaccinated mice compared with the nonvaccinated mice.
The strength of the new vaccine lies in its specificity, says Dr. Cao. The antigen on the vaccine stimulates a very specific response from T cells, which enables the destruction of beta-amyloid but prevents activity that could cause autoimmunity. “[…] it provides strong immunomodulatory effects without inducing an unwanted, vaccine-associated autoimmune reaction in the aging mice,” he says.
Going forward, the team hopes that the vaccine could serve to stop the progression of Alzheimer’s disease in humans, although further studies will be necessary to confirm that the vaccine can produce long lasting antibodies and is safe to use in people.
It is important to note that this study used a mouse model of Alzheimer’s disease. There is a sharp fall-off in translation from animal models to human treatments from many promising preclinical studies, ranging from 0% to 100% failure.
Also, there has been some debate about the effectiveness of targeting beta-amyloid rather than either focusing on the tau protein, launching a combined attack on both proteins, or dampening the inflammation that results in cellular damage.
Beyond Alzheimer’s disease, the researchers suggest that the vaccine type could help improve the immune system of people with other age-related disorders. The vaccine may “lay the foundation for future immunotherapies for aging-related disorders,” the authors conclude.