From July 26 to 30, the 2021 the Alzheimer’s Association International Conference (AAIC) 2021 was convened in Denver, the US. Combining both online and offline forms, the event brought together the world's leading basic science and clinical researchers, clinicians, and nursing research groups, attracting more than 11,000 attendees and over 3,000 scientific presentations to share and exchange newest research findings on the prevention, diagnosis and treatment of Alzheimer's disease (AD) and other dementias.

AAIC 2021 also published a number of research reports and data, including that the number of people with dementia will nearly triple to more than 152 million by 2050 – anticipated trends in smoking, high body mass index and high blood sugar are predicted to increase prevalence by 6.8 million cases, while positive trends in global education access are expected to decrease dementia prevalence worldwide by 6.2 million cases.

“As the leading voluntary health organization in Alzheimer’s research, care and support, the Alzheimer’s Association believes we’re living in a new era of advancement. We’re seeing at AAIC this year dozens of novel treatment approaches that are gaining momentum in clinical trials,” said Maria C. Carrillo, Ph.D., Alzheimer’s Association chief science officer. “Alzheimer’s is a complex brain disease, and very likely will need multiple treatment strategies that address the disease in several different ways along the length of its course. These treatments, once discovered and approved, may then be combined into powerful combination therapies.”

Changes in Gut Microbiota Contribute to AD Progression

Alzheimer’s disease is a slowly progressive and multifactorial disease, with complex pathological mechanisms. For a long time, AD was considered to be a disorder exclusive to the brain that has no relationship to other parts or organs of the body, but the perception of the disease is now shifting from local to holistic treatment approaches.

After holding a special session on the impact of the gut microbiota on AD for the first time in 2020, this year’s AAIC further advanced the topic, by staging the “The Interplay of Systemic Factors in Alzheimer‘s Disease” thematic session and the “Green Memory” investigator meeting on July 27. For the sessions, a number of Chinese and international experts were invited to conduct in-depth discussions, who also shared latest findings to reveal the relationship between AD and the gut microbiota.

Among them, Professor Geng Meiyu, Academic Director General of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, presented her reported titled Landscape Features of Systemic Insults across Alzheimer’s Disease Continuum. For a deeper understanding of AD pathogenesis, the research team adopted an integrative multi-omics strategy, which covered the whole AD continuum from SCD (Subjective Cognitive Decline), aMCI (amnestic Mild Cognitive Impairment), mmAD (mild-to-moderate Alzheimer's disease) to msAD (moderate-to-severe Alzheimer's disease), and used a holistic view of linking the clinical assessments that include those of cognition test and neural imaging, to the systemic insults that include the blood changes and microbial changes.

“We found that systemic insults including neuroendocrine dysregulation, pro-inflammation, metabolic disorders and gut microbiota dysbiosis were engaged across the AD continuum, while such systemic insults were identified preceding brain structural damage, implicating that the first trigger for AD may initiate from the periphery.” Noted Professor Geng.

Gut Microbiome Is Becoming a New Trend in AD Research

In recent years, more and more studies have shown that the gut microbiota, as the “second genome” of human body, plays a very important role in the occurrence and progression of many complex diseases. And the discussions at AAIC 2021 further explored and revealed its relationship with AD.

Professor David M. Holtzman, Chair of the Department of Neurology at Washington University in St. Louis, shared findings from experiments on mice that contain different human APOE genotypes. “Our results indicate that tau-mediated neurodegeneration occurs in an APOE- and APOE isoform-dependent manners and is influenced by the gut microbiota and gender. A certain subpopulation of the innate immune system might be involved in the microbiome-associated regulation of neurodegeneration.”

At the “Green Memory” investigator meeting, Jeffrey Cummings, winner of the Bengt Winblad Lifetime Achievement Award (2018) from the Alzheimer’s Association and Professor at the Cleveland Clinic Lou Ruvo Center for Brain Health, pointed out: “More and more studies have found the gut microbiome’s relationship with inflammation and its implication to neurodegenerative diseases, such as alterations of pro-inflammatory cytokines in the gut microbiome of patients with Parkinson’s disease, and changes in gut microbiota composition during the course of amyotrophic lateral sclerosis (ALS).”

“Gut microbiome is rising as a new trend in AD research,” he added. “If we look at the current R&D pipeline of AD drugs, gut microbiome, which used to be an unusual pathway, is becoming more and more of a usual pathway.”

For GV-971, an AD drug typical of a mechanism of action (MOA) that targets the gut microbiota and the gut-brain axis, Cummings commented on its MOA: by reconditioning the gut microbiota, GV-971 can inhibit the abnormal increase of specific metabolites and reduce peripheral and central inflammation, thereby slowing neurodegeneration.

“The research progress of Green Memory (GV-971’s global Phase III clinical study) is critical,” remarked Professor Cummings.