The American Heart Association’s Basic Cardiovascular Sciences Annual Conference in 2023, recently held in Boston, USA, featured a study indicating that a novel vaccine targeting inflammatory brain cells associated with Alzheimer’s disease may be a key to preventing or altering the course of the disease.
As cells enter an aging state, they release pro-inflammatory factors, leading to various age-related diseases. Previous research identified a new protein, Senescence-Associated Glycoprotein (SAGP), as a biomarker for cellular aging. Inflammatory processes in cells can overactivate SAGP, and increased SAGP activity, in turn, triggers signs of Alzheimer’s disease, including the accumulation of amyloid plaques. Amyloid plaque deposits weaken the brain’s ability to process language, solve problems, and maintain attention.
Researchers at Juntendo University in Tokyo, Japan, developed a vaccine that can eliminate senescent cells expressing SAGP, which has shown promise in improving various age-related diseases, including atherosclerosis and type 2 diabetes in mice. Another study found high expression of SAGPs in the glial cells of Alzheimer’s disease patients.
Researchers created an Alzheimer’s disease mouse model that mimics the human brain and simulates β-amyloid-induced Alzheimer’s disease pathology. To test the efficacy of the SAGP vaccine, mice received either a control vaccine or the SAGP vaccine at 2 and 4 months of age.
The study results revealed that:
The SAGP vaccine significantly reduced amyloid protein deposition in the brain tissue of the cortex, responsible for language processing, attention, and problem-solving.
Mice receiving the vaccine exhibited reduced size in their astrocytes, a type of glial cell. Other inflammatory biomarkers also decreased, suggesting that brain inflammation improved after SAGP vaccine injections.
Behavioral tests (maze-like apparatus) on six-month-old mice showed that those receiving the SAGP vaccine had better responses to their environment compared to mice receiving the placebo vaccine. Mice vaccinated with SAGP often behaved more like normal, healthy mice and displayed greater awareness of their surroundings.
SAGP protein was found to be located very close to specialized brain cells known as microglia, which play a role in the central nervous system’s immune defense. Microglia help clear destructive plaques formed by proteins; however, they can also trigger brain inflammation, damage neurons, and exacerbate cognitive decline in individuals, possibly contributing to the development of Alzheimer’s disease.