TOKYO, JAPAN: Alzheimer's disease is a progressive neurodegenerative disorder characterized by memory loss, cognitive decline, and behavioral changes. It is the most common form of dementia, accounting for 60 to 70 percent of all dementia cases worldwide. The accumulation of amyloid-beta (Aβ) protein deposits in the brain leads to the formation of sticky plaques, disrupting normal brain function and eventually causing the development of tau tangles, which further exacerbates cognitive decline. Recent breakthroughs in Alzheimer's research, such as the approval of Leqembi and promising results from Donanemab trials, have provided hope for slowing disease progression. However, these treatments have limitations, and a vaccine targeting the root cause of Alzheimer's, such as the SAGP vaccine, is a promising approach to halt the disease's progression.
Is there a vaccine for Alzheimer's?
The novel Alzheimer's vaccine, currently under investigation at Japan's Juntendo University, targets senescence-associated glycoprotein (SAGP), which is found on the outer membrane of damaged or "senescent" cells. The vaccine aims to harness the immune system's potential to recognize and eliminate these senescent cells, which are associated with Alzheimer's pathology. By specifically targeting SAGP, the vaccine aims to halt the accumulation of toxic amyloid plaques, which are believed to contribute to the death of brain cells. "If the vaccine could be successful in humans, it would be a big step towards delaying disease progression or even prevention of this disease," said lead study author Chieh-Lun Hsiao, PhD, a post-doctoral fellow in the department of cardiovascular biology and medicine at Juntendo University Graduate School of Medicine in Tokyo, as quoted by the American Heart Association.
The research team conducted preclinical studies in mice with mutated amyloid precursor protein genes, mimicking the key pathological feature of Alzheimer's disease. Some mice received the SAGP vaccine, while others received a placebo. The vaccine was administered to the mice at two and four months of age to examine its impact on disease progression.
Mechanism
The SAGP vaccine works by priming the immune system to recognize and attack senescent cells presenting SAGP on their surfaces. Once the immune system identifies these cells as harmful invaders, it launches an attack against them, effectively eliminating the senescent cells. As a result, the vaccine reduces the burden of both SAGP and amyloid deposits in critical brain regions responsible for language processes, attention, and problem-solving.
Beyond amyloid reduction, the SAGP vaccine showed promising effects on behavioral and cognitive outcomes. The vaccinated mice exhibited behavior similar to healthy mice and demonstrated increased awareness of their surroundings compared to the untreated mice. This suggests that the vaccine not only targets the underlying pathological process but also mitigates cognitive decline associated with Alzheimer's disease. "Alzheimer’s disease now accounts for 50% to 70% of dementia patients worldwide," Dr Hsiao said. "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. 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," he added.
Implications for human trials
While the preclinical results are highly encouraging, it is important to acknowledge that the research is still in its early stages. Human trials involving the SAGP vaccine will require meticulous testing and evaluation for safety, efficacy, and potential side effects. The translation of promising preclinical results to human subjects represents a critical step in the development of novel treatments for Alzheimer's disease.
The mechanisms driving Alzheimer's disease are complex and not fully understood. Although amyloid plaques have been a central focus of research, some experts believe that tau tangles and other factors play a crucial role in disease progression. Therefore, additional studies are necessary to elucidate the intricate interplay between different pathological features and to identify potential therapeutic targets.
Collaborative efforts and backing
The research on the SAGP vaccine is a collaborative effort by a team of experts in the field of Alzheimer's and neuroscience, spearheaded by Dr Chieh-Lun Hsiao. The study has garnered support from the influential American Heart Association, underscoring the significance and potential impact of this research in the fight against Alzheimer's disease.
The successful development of the SAGP vaccine for Alzheimer's disease would represent a groundbreaking achievement. However, it is essential to acknowledge that medical research is iterative, and potential limitations and challenges may arise during the course of human trials. Researchers must remain diligent in addressing these challenges to advance the understanding and treatment of Alzheimer's disease.
