The gut microbiome (GMB) is comprised of trillions of microorganisms that reside in the intestinal tract. Evidence suggests that the bacterial composition of the GMB is altered in Alzheimer’s disease patients compared to healthy controls (some species increase in abundance while others decrease); a finding that has also been observed in some mouse models of AD. Recent studies suggest that changes in the gut microbiome may directly contribute to the development of Alzheimer’s disease. Mechanisms that may mediate this link are still mostly unknown. Early research is beginning to identify potential routes by which changes in the gut can impact the brain and pathologies related to Alzheimer’s disease such as amyloid plaque deposits. Some areas of focus include the disruption of the entire ecosystem or a role for specific resident microbes, peripheral inflammation that impacts the brain through interactions with the vasculature or the brain’s resident innate immune cells (glia), and even the direct spread of microbes from the gut to the brain.

The projects of this consortium represent a multi-faceted approach to investigating the mechanisms by which the microbiome impacts AD progression. The projects of this consortium will increase the field’s understanding of this important emerging area and its relevance to developing novel therapeutics for people who might develop or who are living with Alzheimer’s disease.

 

MICROBIOME CONSORTIUM: CURRENTLY FUNDED RESEARCHERS

Robert Vassar, Ph.D., Northwestern University Feinberg School of Medicine; Chair of the CureAlz Microbiome Consortium

David Holtzman, M.D., Washington University School of Medicine in St. Louis

Laura M. Cox, Ph.D., Brigham and Women’s Hospital; Harvard Medical School

Sangram S. Sisodia, Ph.D., University of Chicago

Rudolph Tanzi, Ph.D., and Nanda Kumar Navalpur Shanmugam, Ph.D., Massachusetts General Hospital; Harvard Medical School

 

MICROBIOME CONSORTIUM: CURRENTLY FUNDED PROJECTS 

Interaction of the Microbiome with Astrocytes and Amyloid Pathology:  Robert Vassar, Ph.D., $690,000

The Role of Gut Microbial Metabolism in Tau-Mediated Neurodegeneration: David Holtzman, M.D., $575,000

Harnessing Diet-Microbe Interactions to Prevent Alzheimer’s Disease Pathogenesis: Laura M. Cox, Ph.D., $563,000

Temporal Relationships Between Gut Dysbiosis, Brain Amyloid Beta Metabolism and Microglia Cell Activation Following Antibiotic Treatment: Sangram S. Sisodia, Ph.D., $500,000

Microbial Profiling of Human Brain and Gut Microbiomes in Alzheimer’s Disease: Rudolph Tanzi, Ph.D., and Nanda Kumar Navalpur Shanmugam, Ph.D., $575,000

 

MICROBIOME CONSORTIUM: PUBLISHED PAPERS 

Chandra, S., & Vassar, R. J. Gut microbiome-derived metabolites in Alzheimer’s disease: Regulation of immunity and potential for therapeutics, Immunological Reviews, October 24, 2024, Read More

Chandra, S., & Vassar, R. The role of the gut microbiome in the regulation of astrocytes in Alzheimer’s disease, Neurotherapeutics, July 24, 2024, Read More

Zhu, Y., Self, W. K., & Holtzman, D. M. An emerging role for the gut microbiome in tauopathy, Neurotherapeutics, July 3, 2024, Read More

Wasén, C., Beauchamp, L. C., Vincentini, J., Li, S., LeServe, D. S., Gauthier, C., Lopes, J. R., Moreira, T. G., Ekwudo, M. N., Yin, Z., da Silva, P., Krishnan, R. K., Butovsky, O., Cox, L. M., & Weiner, H. L. Bacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer’s disease mouse models, Nature Communications, May 8, 2024, Read More