New vaccine alleviates Alzheimer’s in mice, suggesting human benefits

BOSTON (CN) — A new vaccine could help delay or prevent the symptoms of Alzheimer’s disease, according to preliminary research presented at the American Heart Association’s Basic Cardiovascular Sciences Scientific Sessions in Boston.

Using mice as test subjects, the vaccine eliminates senescent cells expressing senescence-associated glycoprotein (SAGP). Senescent cells are those that stop multiplying and don’t die off when they’re supposed to; their accumulation is considered to contribute to Alzheimer’s, Type 2 diabetes and certain cancers.

For the study, researchers created an Alzheimer’s disease mouse model that mimics the human brain and simulates the progression of Alzheimer’s disease pathology. Mice were separated into two groups: One would receive a control vaccine while the other group would get the SAGP vaccine. Shots were given when the mice were two months old and fourth months old.

After being vaccinated, the mice that received the SAGP vaccine showed fewer amyloid plaques, less brain inflammation and improvements to their awareness and behavior.

Amyloid plaques are misfolded proteins that form in the spaces between nerve cells. These proteins are thought to play a central role in Alzheimer’s disease.

“Alzheimer’s disease now accounts for 50% to 70% of dementia patients worldwide. Our study’s novel vaccine test in mice points to a potential way to prevent or modify the disease. The future challenge will be to achieve similar results in humans,” said the study’s lead author Chieh-Lun Hsiao, a postdoctoral fellow in the department of cardiovascular biology and medicine at Juntendo University Graduate School of Medicine in Tokyo. “If the vaccine could prove to be successful in humans, it would be a big step forward towards delaying disease progression or even prevention of this disease.”

By the six-month mark, mice that received the SAGP vaccine showed more awareness in their surroundings and had more careful behavior than the control group mice, according to the research. Notably, the mice that received the SAGP vaccine exhibited signs of anxiety; this is notable because anxiety is a sign that a creature is aware of its environment. According to the researchers, humans in the late stages of Alzheimer’s disease do not experience anxiety because they are not fully aware of the world around them. The presence of anxiety in the mice could be a sign of alleviated symptoms.

SAGP-vaccinated mice also performed significantly better than control group mice in maze tests.

Several inflammatory biomarkers of Alzheimer’s disease were also observed, including a reduction of amyloid deposits in brain tissue in the cerebral cortex. The cerebral cortex is responsible for language processing, attention and problem solving.

Glial cells were shown to be reduced in size in mice that received the vaccine, implying that brain inflammation was improved with the vaccine. 

“Earlier studies using different vaccines to treat Alzheimer’s disease in mouse models have been successful in reducing amyloid plaque deposits and inflammatory factors, however, what makes our study different is that our SAGP vaccine also altered the behavior of these mice for the better,” Hsiao said.

The vaccine was previously developed by researchers at Juntendo University Graduate School of Medicine in Tokyo. The vaccine was shown to improve age-related illnesses, including atherosclerosis and Type 2 diabetes in mice.  A different study found that SAGPs were highly expressed in the glial cells of people suffering from Alzheimer’s disease. Knowing this, the researchers tested the vaccine in mice to target SAGP-overexposed cells to treat Alzheimer’s disease.

According to the researchers, previous research suggested that the SAGP protein is highly present in microglia. Microglia are specialized brain cells that play a role in defending the central nervous system. They can help clear plaque formed by proteins, but they can also trigger brain inflammation that can damage neurons or hinder cognitive ability. Therefore, microglia are very important cells to target in people with Alzheimer’s disease.

“By removing microglia that are in the activation state, the inflammation in the brain may also be controlled. A vaccine could target activated microglia and remove these toxic cells, ultimately repairing the deficits in behavior suffered in Alzheimer’s disease,” Hsiao said.

According to the 2023 American Heart Association Statistical Update, nearly 4 million Americans over the age of 30 suffered from Alzheimer’s disease in 2017. Instances of Alzheimer’s disease are expected to increase, with 9.3 million sufferers projected by 2060.

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