A Possible New Vaccine to Treat Alzheimer’s? It Worked in Mice

A novel vaccine could help fix damage in the brain caused by Alzheimer’s disease or even prevent it, according to new research.

Preliminary findings presented at the American Heart Association’s Basic Cardiovascular Sciences Scientific Sessions 2023 in Boston this week  found that when mice brains were transformed to create Alzheimer’s disease-like qualities and then given the new vaccine, toxic Alzheimer’s-related proteins and inflammation decreased. 

Additionally, the vaccine appeared to improve the behavior of the mice, which could reflect a diminishment of the disease, the researchers reported.

“Our study’s novel vaccine test in mice points to a potential way to prevent or modify the disease,” Chieh-Lun Hsiao, Ph.D., a fellow at Juntendo University Graduate School of Medicine in Tokyo who led the experiments, said in a statement.

“The future challenge," she added, "will be to achieve similar results in humans."

There have been many therapies that have shown promise in mice that have not turned into effective treatments for humans with Alzheimer’s – a disease that some 5.8 million Americans were living with as of 2020, according to the Centers for Disease Control and Prevention. Alzheimer’s is the most common form of dementia, and experts say that case numbers will only continue to rise in coming years. 

As with other similar types of research, the findings from this most recent study will now need to be reproduced in other models, and by scientists in other labs for verification, Thomas Wisniewski, M.D., director of NYU Langone’s Alzheimer’s Disease Research Center, who is  not involved in the current study, told The Messenger. 

"This is at least years away to know if it is a viable, promising approach," Dr. Wisniewski said. "Much more work needs to be done to reproduce this line of investigation."

Still, the research is “intriguing,” he said, noting that this area of studying issues associated with senescence – the process of cells or a person getting older – “is an understudied area.”

“It’s nice to see more work being done in this area," he continued, "because these sorts of approaches, if successful, are applicable to multiple neurodegenerative disorders, not just  Alzheimer's disease.” 

Researchers from the same university in Tokyo currently at work on this vaccine had previously developed a vaccine that improved age-related diseases including atherosclerosis and Type 2 diabetes in mice. 

The vaccine eliminated senescent cells – aging cells that can release inflammation-triggering chemicals – which were expressing senescence-associated glycoprotein (SAGP). 

Another study also found that SAGPs are highly expressed in the glial cells of people with Alzheimer’s disease. Glial cells, which make up a large part of the brain, provide connective and protective functions.

Based on these findings, Hsiao and her colleagues tested the vaccine in mice to target SAGP-overexpressed cells to treat Alzheimer’s disease.

The researchers created an Alzheimer’s disease mouse model that mimics a human brain and simulates amyloid-beta-induced Alzheimer’s disease pathology. Amyloid is a protein that can clump together and form toxic plaques in people with Alzheimer’s.

To test the SAGP vaccine’s efficacy, the mice were treated with a control vaccine or the SAGP vaccine, and given a dose at two and four months old.

Usually, people in the late stage of Alzheimer’s lack anxiety, which means they are not aware of the things around them, according to the researchers.  

The mice which received the SAGP vaccine had anxiety, meaning they were more cautious and more aware of things around them – a sign researchers say could indicate a lessening of the disease. 

In addition, several inflammatory biomarkers of Alzheimer’s disease were also reduced, including a significant lowering of amyloid deposits in brain tissue located in the cerebral cortex region, which is responsible for language processing, attention and problem solving.

When the mice reached six months, those who received the SAGP vaccine and performed a behavior test in a maze-type device responded much better to their environment than the mice who received the placebo vaccine. 

The SAGP-vaccinated mice tended to behave like healthy mice and exhibited more awareness of their surroundings, Hsiao and her colleagues found.

Earlier this month, other researchers presented their latest findings at the Alzheimer’s Association's annual conference in Amsterdam, where some of the world’s leading experts on the devastating disease gathered.

Perhaps the most exciting revelation from the conference came  from Eli Lilly. The American pharmaceutical company revealed phase 3 trials results of a proposed Alzheimer’s treatment, donanemab, finding it could slow progression of the disease by 35%.