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Bile Acids Provide More Evidence of the Gut Microbiome’s Effect on Alzheimer’s Disease

Alzheimer's disease researcher Dr. Priyanka Baloni

Alzheimer’s disease researcher Dr. Priyanka Baloni is the lead author of a paper published in the journal Cell Reports Medicine.

More than 5 million Americans are living with Alzheimer’s disease, and that number is expected to nearly triple by 2050. Alzheimer’s is the sixth leading cause of death in the U.S., yet treatments for it and other forms of dementia are largely ineffective. To date, there have been an estimated 400 trials and experimental Alzheimer’s treatments that have failed, suggesting there is limited understanding of the mechanisms of the disease.

ISB researchers and their collaborators are looking beyond the one-drug, one-solution approach that has thus far failed. Instead, they are focusing on other promising research avenues, such as the possible role of the gut microbiome in Alzheimer’s disease. This line of research has uncovered compelling findings that were recently published in the journal Cell Reports Medicine

ISB is part of the Accelerating Medicines Partnership – Alzheimer’s Disease (AMP-AD), a collaborative project funded by the National Institute on Aging. The study team examined about 1,000 post-mortem brain samples and compared the metabolomics of 111 brain samples, and found a difference in the type of bile acids in cognitively normal brains vs. those showing cognitive decline. The findings suggest that secondary bile acids may be associated with dementia. (Some bile acids have been shown to be neuroprotective, while others – secondary bile acids – are categorized as toxic to living cells.)

“Using a systems biology approach, we identified alterations in cholesterol and bile acid metabolism in Alzheimer’s disease,” said Dr. Priyanka Baloni, an ISB senior research scientist and lead author of the paper. “Our study provides evidence of genes in alternative bile acid and neural cholesterol clearance pathways expressed in the brain along with the role of taurine and bile acid transporters, suggesting that there is a deeper connection between the brain-gut axis in Alzheimer’s.”

Laying the groundwork

Bile acids are also being studied in mood disorders, depression, Parkinson’s and other neurodegenerative diseases. And pharma companies are investing in developing drugs to target bile acids that are known to be toxic to cells. 

The team also showed – for the first time – brain region-specific metabolic networks that can be further studied by the research community. 

“We are laying the groundwork for understanding how the brain may influence the microbiome and vice versa. For a complex disease like Alzheimer’s, where lifestyle choices such as diet, exercise and regular sleep have an established role in disease etiology, understanding the relationship to the microbiome is critical,” said Dr. Cory Funk, an ISB senior research scientist who contributed to this work. 

ISB, along with a collaborative network of partners, is pioneering a multimodal approach that combines personal data, lifestyle factors, cognitive training and systems medicine, and is rigorously testing these new approaches. The goal for this work is to prevent, slow, and even reverse many neurological conditions before they become irreversible.

Brain health is the topic of ISB’s virtual “Reimagine” event taking place December 9. Reimagine will focus on ISB’s unique approach to studying and treating Alzheimer’s and other diseases. You are invited to get an insider’s look at our latest clinical trial and to learn what you can start doing today to improve your own brain health. Learn more and register here.

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