A new vaccine, discussed at the American Heart Association’s Scientific Sessions 2023, may have the potential to prevent or modify Alzheimer’s disease by targeting inflamed brain cells linked to the condition. Researchers from Juntendo University Graduate School of Medicine in Japan developed a vaccine that successfully treated age-related diseases in mice by eliminating senescent cells expressing a specific protein called SAGP. Interestingly, SAGP is found in high levels in the glial cells of people with Alzheimer’s disease. Based on these findings, the researchers tested the vaccine on mice to target the overexpressed SAGP cells and treat Alzheimer’s.
The lead study author, Chieh-Lun Hsiao, explained that Alzheimer’s is a major cause of dementia worldwide, affecting 50% to 70% of patients. The vaccine showed promising results in mice, but the real challenge lies in achieving similar outcomes in humans. If successful, this vaccine could be a significant step forward in delaying the progression or even preventing Alzheimer’s.
During the study, the research team created an Alzheimer’s mouse model that mimicked the human brain’s pathology related to the disease. They administered the SAGP vaccine to some mice while others received a control vaccine. The vaccinated mice exhibited less anxiety and showed increased awareness of their surroundings, suggesting a potential improvement in the disease. Additionally, several inflammatory biomarkers associated with Alzheimer’s were reduced.
The vaccine was found to significantly reduce amyloid deposits in the brain’s cerebral cortex region, which is responsible for language processing and problem-solving. Moreover, the size of astrocyte cells, a type of glial cell responsible for inflammation, decreased in mice receiving the vaccine, indicating an improvement in brain inflammation. Behavioral tests showed that mice vaccinated with SAGP responded better to their environment and behaved more like healthy mice.
The study also revealed that the SAGP protein was located near microglia, specialized brain cells involved in immune defense. While microglia help clear harmful plaque in the brain, they can also trigger inflammation, contributing to Alzheimer’s development. The researchers believe that targeting activated microglia with the vaccine could control brain inflammation and improve Alzheimer’s symptoms.
According to the National Institute on Aging, Alzheimer’s is characterized by the accumulation of amyloid beta peptides that form plaques, disrupting brain cell function. Vascular issues may also lead to a compromised blood-brain barrier, preventing necessary nutrients from reaching the brain and clearing away toxic substances like beta-amyloid, resulting in chronic inflammation and Alzheimer’s progression.
Hsiao noted that previous studies using different vaccines for Alzheimer’s showed success in reducing amyloid plaque deposits and inflammatory factors, but their SAGP vaccine also positively influenced the mice’s behavior.
The researchers emphasized that microglia, with their elevated levels of SAGP protein, are crucial targets in treating Alzheimer’s. By removing activated microglia with the vaccine, brain inflammation might be controlled, and the deficits in behavior caused by Alzheimer’s could be improved.
Alzheimer’s disease is a significant health concern, affecting millions of Americans, and its prevalence is projected to increase in the coming decades.
The co-authors, disclosures, and funding sources are listed in the abstract. The American Heart Association receives funding from various sources, including individuals, foundations, corporations, and pharmaceutical companies, but strict policies are in place to prevent any influence on the scientific content of their research.