Research Spotlight: Establishment of a Consensus Protocol to Explore the Brain Pathobiome

William Eimer, PhD, and Rudolph Tanzi, PhD, from the Department of Neurology at Massachusetts General Hospital, are among the authors of a recently published paper in Alzheimer’s & Dementia, Establishment of a Consensus Protocol to Explore the Brain Pathobiome in Patients With Mild Cognitive Impairment and Alzheimer’s Disease

What Question Were You Investigating?

What role do germs in the brain play in the onset of Alzheimer’s disease and other types of dementia?

Scientists have identified germs in the brain, but few definitive conclusions have been reached about their role in Alzheimer’s disease.

Studies point to many different types of viruses, bacteria, fungi and parasites in the brains of healthy people and those with neurological diseases like Alzheimer’s.

Due to inconsistent methods and results at different labs around the world, we are addressing the issue of variation in these experiments to develop accurate and refined protocols.

The Alzheimer’s Pathobiome Initiative (AlzPI) is an international collaboration that will identify the best method or methods for finding these microbes in the brain.

Using samples that we can safely collect from living patients (blood, saliva etc.), we will use these tools to identify germs that may play a causal role in neurological diseases such as Alzheimer’s and other forms of dementia.

This may lead the development of targeted treatments for patients that have an infection (germs) driving their individual case of dementia.

Increasing evidence has suggested a role for microbial pathogens and infection in the etiology and neuropathogenesis of Alzheimer’s disease.

There exist significant levels of variability and major discrepancies across scientific studies attempting to determine the presence of microbes in the brain and how microbial diversity may differ in the post-mortem brains of Alzheimer’s patients and age-matched unaffected elderly subjects.

What methods or approach did you use?

We reviewed the literature on different detection methods as well as the research available on various bio-samples (including post-mortem brain) to help develop an accurate consensus protocol.

Additionally, we identified case reports of “reversible dementia,” in which microbial infection was deemed the primary driver of dementia.

In these cases, the majority of patients had a robust clinical response to tailored antimicrobial therapy, many of them returning to normal levels of cognition.

Standardization of next-generation sequencing techniques for the identification of microbes will be essential for accurate and reproducible analysis of their roles in disease pathology.

coordinated, interdisciplinary, international collaboration to refine these protocols has never been undertaken before.

What Are the Clinical Implications?

This paper outlines a ground-breaking collaborative effort to standardize the discovery of microbes in the brain and to determine whether they are merely correlated with Alzheimer’s disease and other neurodegenerative diseases—the result of lifestyle exposure conditions of elderly bed-ridden patients—or whether they actually contribute to the etiology of neurodegenerative disease.

This collaborative poses to more effectively and reliably identify roles for pathogenic microbes in neurological disorders. Success in this endeavor would lead to a significant shift in both preventative and acute treatment for these diseases.

The Alzheimer’s Pathobiome Initiative roadmap will establish a framework that can and should be used to study the relationship between microbes and a host of chronic inflammatory diseases both within and beyond the brain.

Paper Cited:

Lathe, R., Schultek, N. M., Balin, B. J., Ehrlich, G. D., Auber, L. A., Perry, G., Breitschwerdt, E. B., Corry, D. B., Doty, R. L., Rissman, R. A., Nara, P. L., Itzhaki, R., Eimer, W. A., Tanzi, R. E., & Intracell Research Group Consortium Collaborators (2023). Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease: Research outline and call for collaboration. Alzheimer's & dementia : the journal of the Alzheimer's Association, 10.1002/alz.13076. Advance online publication. https://doi.org/10.1002/alz.13076

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2021, Mass General was named #5 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.