This new vaccine targets senescence-associated glycoprotein (SAGP), which is expressed in inflamed brain cells linked to Alzheimer’s disease. Tested in mice, the vaccine reduced amyloid deposits, decreased inflammatory biomarkers and even improved awareness of one’s surroundings.
The results of this preliminary research offer promising implications for the future treatment of Alzheimer’s in humans.
Highlights
The new vaccine targets senescence-associated glycoprotein (SAGP) overexpressed in inflamed brain cells associated with Alzheimer’s disease.
Tests in mice have shown that the vaccine reduces amyloid deposits and decreases inflammatory biomarkers linked to Alzheimer’s disease.
The mice that received the vaccine showed increased awareness of their surroundings, suggesting a reduction in disease symptoms.
According to preliminary research presented at the American Heart Association’s Basic Cardiovascular Sciences Scientific Sessions 2023, a new vaccine that targets inflamed brain cells associated with Alzheimer’s disease could hold the key to preventing or changing the course of the disease.
The meeting will be held in Boston from July 31 to August 3, 2023 and will offer the latest research on innovations and discoveries in the field of cardiovascular sciences.
Previously, researchers at Juntendo University Graduate School of Medicine in Tokyo, Japan developed a vaccine to kill senescent cells expressing senescence-associated glycoprotein (SAGP) – a senolytic vaccine that improved several age-related diseases. , including atherosclerosis and type 2 diabetes in mice. Another study also found that SAGPs are highly expressed in the glial cells of people with Alzheimer’s disease.
Based on the results of these studies, the researchers tested this vaccine in mice to target overexpressed SAGP cells and treat Alzheimer’s disease.
“Alzheimer’s disease now accounts for 50%-70% of dementia patients worldwide. The new vaccine tested in mice by our study points to a potential way to prevent or modify the disease. The future challenge will be to obtain similar results in humans,” said lead study author Chieh-Lun Hsiao, Ph.D., a fellow in the department of cardiovascular biology and medicine at Juntendo University Graduate School of Medicine in Tokyo. .
“If the vaccine turns out to be effective in humans, it would be a big step towards delaying the progression of the disease or even preventing it.”
In this study, the research team created a mouse model of Alzheimer’s disease that mimics the human brain and mimics the pathology of Alzheimer’s disease induced by beta amyloid.
To test the effectiveness of the SAGP vaccine, mice were given either a control vaccine or the SAGP vaccine at two and four months of age. Usually, people in the advanced stage of Alzheimer’s are anxiety-free, which means they are unaware of the things around them.
The mice that received the vaccine had anxiety, meaning they were more cautious and more aware of things around them – a sign that the researchers say could indicate a decrease in the disease. In addition, several inflammatory biomarkers of Alzheimer’s disease were also reduced.
The study found that:
The SAGP vaccine significantly reduced amyloid deposits in brain tissue located in the cerebral cortex region responsible for language processing, attention and problem solving.
The astrocyte cell (the most abundant glial cell type in the brain and a specific inflammatory molecule) was found to decrease in size in the mice that received the vaccine. Reductions in other inflammatory biomarkers were also observed, implying that brain inflammation improved in response to the SAGP vaccine.
A behavioral test (maze device) on mice at six months of age revealed that those given the SAGP vaccine responded significantly better to the environment than those given the placebo vaccine. The SAGP vaccinated mice tended to behave like normal healthy mice and showed greater awareness of their surroundings.
The SAGP protein has been shown to be found in very close proximity to specialized brain cells called microglia, which play a role in the immune defense of the central nervous system. Microglia help clear harmful plaques formed by proteins, but they also trigger inflammation in the brain that can damage neurons and worsen a person’s cognitive decline, which could be one of the causes of developing Alzheimer’s disease.
According to the National Institute on Aging, a division of the National Institutes of Health, in Alzheimer’s disease a buildup of brain proteins called amyloid beta peptides clumps into plaques that collect between neurons and disrupt cellular function.
Vascular problems can also lead to disruption of the blood-brain barrier, which usually protects the brain from harmful agents and allows access for glucose and other necessary inputs.
This faulty blood-brain barrier prevents glucose from reaching the brain and prevents the disposal of beta-amyloid and toxic proteins, resulting in chronic inflammation and progression of Alzheimer’s disease.
“Previous studies using different vaccines to treat Alzheimer’s disease in mouse models were successful in reducing amyloid plaque deposits and inflammatory factors, but what makes our study different is that our SAGP vaccine also altered behavior of these mice for the better,” Hsiao said.
According to the researchers, previous research suggests that the SAGP protein is very elevated in microglia, meaning that microglia are very important cells to target in Alzheimer’s disease.
Hsiao said: “By eliminating microglia that are in an activated state, inflammation in the brain can also be controlled. A vaccine could target activated microglia and remove these toxic cells, ultimately repairing the behavioral deficits of Alzheimer’s disease.”
According to the American Heart Association’s 2023 Statistical Update, approximately 3.7 million Americans, ages 30 and older, had Alzheimer’s disease in 2017, and this number is projected to increase to 9.3 million. by 2060.
The coauthors, their disclosures, and funding sources are listed in the abstract.
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