They test a vaccine that prevents the impact of Alzheimer’s on the brain

Dementia currently affects more than 55 million people and the Alzheimer disease It is the most frequent cause (it constitutes around 60-70% of all cases), according to the World Health Organization (WHO). In the elderly there is a greater chance of developing Alzheimer’s, so the prevalence of the disease is increasing with the aging of the population.

Scientists are trying to find drugs capable of preventing or delaying the onset of this dementia that drastically impairs the quality of life of patients and their families. now a new experimental vaccine that targets inflamed brain cells linked to Alzheimer’s could prevent or alter the course of the diseaseaccording to preliminary study results presented at the American Heart Association’s Basic Cardiovascular Sciences 2023 Scientific Sessions.

“Alzheimer’s disease now accounts for between 50% and 70% of dementia patients worldwide. New vaccine evidence from our mouse study points to a potential way to prevent or modify disease. The future challenge will be to achieve similar results in humans,” said the study’s lead author, Chieh-Lun Hsiao, Postdoctoral Fellow in the Department of Biology and Cardiovascular Medicine, Juntendo University School of Medicine in Tokyo, Japan. “If the vaccine could prove successful in humans, it would be a big step forward in slowing the progression of the disease, or even preventing it.”

How the new Alzheimer’s vaccine works

The new research built on previous ones, such as one carried out by researchers at the Juntendo University School of Medicine who developed a vaccine to eliminate senescent cells that express senescence-associated glycoprotein (SAGP), which ameliorated diseases related to age, such as atherosclerosis and type 2 diabetes in mice. Another previous study found that SAGPs are highly expressed in the glial cells of people with Alzheimer’s.

“Previous studies of Alzheimer’s vaccines in mouse models have reduced amyloid plaque deposits, but our SAGP vaccine also altered the behavior of these mice for the better.”

The authors of the new work took these findings into account and tested their vaccine in mice with the aim of attack overexpressed cells with SAGP to treat Alzheimer’s disease. To do this, they designed a mouse model with Alzheimer’s that imitates a human brain and simulates the pathology of this disease induced by the accumulation of amyloid beta protein.

The researchers gave the mice either a control vaccine, or the SAGP vaccine, at two and four months of age. Patients in the last stage of Alzheimer’s disease generally do not show anxiety, indicating that they are not aware of what is happening in their environment. However, the mice that received the vaccine were anxious, which means that were more cautious and aware of things around them, something that, according to the researchers, could indicate a reduction of the disease. In addition, several inflammatory biomarkers of Alzheimer’s disease were also decreased.

The main findings of the study are:

  • The SAGP vaccine significantly reduced amyloid deposits in brain tissue located in the area of ​​the cerebral cortex, which is responsible for language processing, attention, and problem solving.
  • Astrocytes – the most abundant glial cells in the brain – and other specific inflammatory molecules decreased in size in the vaccine-treated mice, and a reduction in other inflammatory biomarkers was observed, indicating that inflammation in the brain improved in response to the SAGP vaccine.
  • Mice that received the SAGP vaccine responded significantly better to a maze-type behavioral test at six months of age than those that received the placebo vaccine. SAGP-vaccinated mice tended to behave like normal healthy mice and showed more awareness of their surroundings.

The researchers also found that the SAGP protein is found in close proximity to specialized brain cells called microglia, which play a role in the immune defense of the central nervous system. Microglia help remove harmful plaque made of proteins, but they also contribute to brain inflammation that can deteriorate neurons and aggravate cognitive declinewhich could be one of the causes of the appearance and progression of Alzheimer’s disease.

The beta-amyloid plaques that accumulate between neurons interfere with their functions and form plaques that the body cannot eliminate. Vascular problems can also trigger the breakdown of the blood-brain barrier that protects the brain from harmful agents while allowing access for glucose and other necessary factors. A faulty blood-brain barrier disrupts the flow of nutrients to the brain and prevents the removal of beta-amyloid and toxic proteins, leading to chronic inflammation and the progression of Alzheimer’s disease.

Alzheimer’s vaccines that have been tested in mice in previous studies were able to reduce beta-amyloid plaques and brain inflammation, but the new study stands out because they also has improved the behavior of mice to whom the vaccine has been administered and because it has also shown that microglia play a key role in Alzheimer’s disease and that its control would improve both the development of the disease and its progression.

“Previous 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 it also altered the behavior of these mice for the better,” Hsiao says, adding: “By removing microglia that are in a state of activation, inflammation in the brain can also be controlled. A vaccine could target activated microglia and remove these toxic cellsultimately repairing the behavioral deficits suffered in Alzheimer’s disease”.


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