Experts from China and the United States: "Brain gut Axis" or Common Mechanisms of Cognitive Disorders such as Alzheimer's Disease Drugs | Alzheimer's | Brain gut Axis

Is Alzheimer's disease closely related to the gut? Recently, the Cognitive Impairment and Brain Intestinal Axis Summit Forum was held in Shanghai, and Professor Sangram Sisodia, Director of the Center for Molecular Neurobiology at the University of Chicago, introduced his latest research findings - compared with the experimental control group, the original Chinese Alzheimer's disease drug GV-971 can modify the composition of gut microbiota and reduce the brain's composition β Amyloid plaques.

Clinical experts from the Shanghai Neurology Department believe that this research achievement fills the "mechanism evidence puzzle" of the "brain gut axis" theory in neurodegenerative diseases, providing scientific basis for early diagnosis and drug treatment of neurodegenerative diseases such as Alzheimer's disease. They also provide the public with the need to pay attention to the memory decline of elderly people at home, not to assume it is a normal phenomenon, but to promptly seek medical attention and receive a diagnosis of cognitive impairment.

"Brain gut axis" or applicable to various cognitive disorders

At present, there are at least 50 million Alzheimer's disease patients worldwide, with approximately 10 million new cases added each year. The current number of patients in our country exceeds 10 million, accounting for about one-fifth of the total number of patients in the world. According to literature statistics provided by Liu Xueyuan, Director of the Neurology Department of the Tenth People's Hospital of Shanghai, the proportion of Chinese citizens aged 60 and above with cognitive impairment is 5.3%; The proportion of cognitive impairment patients in urban and rural areas is 1:1.36, and the proportion of male and female patients is 1:1.65. In recent years, the incidence rate of Alzheimer's disease in China has continued to rise, which is higher than that in many European and American countries, bringing a heavy burden of care to families and society.

In the past few decades, scientists have proposed multiple disease mechanism hypotheses for Alzheimer's disease, but the vast majority of drug development based on this has ended in failure. GV-971 is one of the few drugs approved for marketing.

In the process of developing this original new drug, the team led by Geng Meiyu, a researcher at the Chinese Academy of Sciences Shanghai Institute of Materia Medica, discovered the "brain gut axis" mechanism of Alzheimer's disease - systemic disorders including neuroendocrine disorders, proinflammatory, metabolic disorders, and intestinal flora disorders throughout the course of the disease, and these systemic disorders were observed before the occurrence of brain structural damage. This means that the initial trigger for Alzheimer's disease may start with the peripheral nervous system.

The chemical structural formula of GV-971

"The intestine is the organ in the human body with the second highest number of neuronal cells, second only to the brain," Liu Xueyuan explained. "These neurons secrete a lot of biological substances, which affect the inflammatory response in the brain through blood circulation, and may ultimately affect it." β The deposition of amyloid protein Therefore, it can be said that the connection between the gut microbiota and the brain is established through the "brain gut axis". If the gut microbiota is dysregulated, it may cause the brain to β Abnormal metabolism of amyloid protein or enhanced inflammatory response.

In addition to Alzheimer's disease, the "brain gut axis" may also be applicable to other cognitive impairment diseases, such as vascular dementia and cognitive impairment after elevated blood sugar, all of which are related to dysbiosis of the gut microbiota.

In March of this year, Sisodia announced the research results led by him and Professor David Holtzman: Compared with the control group, GV-971 can modify the composition of intestinal microbiota, reducing β Amyloid plaques. The experiment also showed that GV-971 can significantly reduce the activation of microglia and astrocytes, thereby inhibiting the occurrence of neuroinflammation.

Professor Sangram Sisodia gave a speech at the Summit Forum on Cognitive Disorders and Brain Intestinal Axis.

This study replicates and supports the GV-971 therapeutic mechanism published by Geng Meiyu's team in Cell Research, confirming that it can inhibit neuroinflammation and reduce the deposition of Alzheimer's pathological markers in addition to targeting the brain gut axis to affect specific bacterial communities.

Alzheimer's disease needs to be studied and treated from a holistic perspective

"The research of American research teams has guiding significance for the clinical diagnosis, including early diagnosis, of Alzheimer's disease," said Tang Huidong, chief physician of neurology at Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine. "Before the onset of the disease, the gut microbiota in the human body may have begun to become disrupted, so we can use changes in the gut microbiota as an indicator for early diagnosis of Alzheimer's disease, achieving early detection and intervention."

Tang Huidong believes that the pathogenesis of the "brain gut axis" suggests that Alzheimer's disease may not be a single disease, but a syndrome that can be divided into multiple subtypes. "Human beings are a whole, and we cannot study all organs separately, which is also a difference between Western medicine and traditional Chinese medicine. If Alzheimer's disease is a syndrome, we need to study and treat it from a holistic perspective."

Three professors, Sangram Sisodia, Liu Xueyuan, and Tang Huidong, were interviewed.

Regarding the statement that "Alzheimer's disease is a syndrome", Liu Xueyuan agrees: "All cognitive impairment diseases may be syndromes, can we all intervene through the brain gut axis theory?" In his view, there are commonalities between cognitive impairment caused by Parkinson's disease, cognitive impairment caused by blood sugar increase, cognitive impairment after stroke, and Alzheimer's disease. GV-971 based on the pathogenesis of the brain gut axis may have therapeutic effects, so it is necessary to conduct clinical trials in these disease fields. Moreover, in addition to the "brain gut axis" mechanism, GV-971 purified from seaweed may also have other effects, such as antioxidant and free radical scavenging, which have potential therapeutic effects on patients with cognitive impairment.

Liu Xueyuan also wants to remind the public through the media to pay attention to early cognitive impairment and pay attention to the problem of memory decline in the elderly. Once it is discovered that the elderly person's memory has decreased, although their daily living ability has not decreased, family members should also accompany the elderly person to the hospital for treatment. "Go to the hospital for a screening to see if there is any pathological memory impairment and if it has reached the level of treatment needed. The public should also pay attention to post-stroke cognitive impairment. If elderly people experience cognitive impairment after a stroke and do not receive timely treatment, it can also affect the treatment effect of the stroke itself."