Researchers receive 9.5 million grant to study relationship between polyphenol intake, Alzheimer’s and the brain-gut-microbiome system

UCLA Health researchers, in collaboration with researchers from the Republic of Ireland and Northern Ireland, have received $9.5 million award from the National Institutes of Health (NIH) with support from European funding agencies — The Science Foundation Ireland (SFI) and the Public Health Agency Health & Social Care (HSC) — to study the effects of polyphenols on cognitive health and the brain-gut microbiome system.

The proposal, named MAEVE, stands for “Microbiota mediated flavonoid metabolites for cognitive health.”

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In this interdisciplinary and multicenter study funded through the Tripartite US-Ireland Research & Development Partnership Program, researchers will investigate the impact of dietary polyphenol supplements on 300 older adults at-risk for Alzheimer’s disease. Polyphenols — a key component of Mediterranean diets and found in berries, grapes, green tea, and cocoa — may delay cognitive decline by preserving brain function and structure through gut microbiome metabolites by altering the physiology of the host’s secondary bile acids, highlighting their potential role in Alzheimer’s disease prevention.

Cognitive decline

“It’s a multicenter, longitudinal, and translational intervention study designed so that we can look at the mechanisms and pathways involved in cognitive decline,” said Aparna Church, PhD, co-director of the UCLA Goodman-Luskin Microbiome Center and principal investigator. “We’re looking at multiple markers such as cognitive functioning, brain structure and function, the microbiome and microbial polyphenol metabolites, inflammatory markers like interleukins, and Alzheimer’s disease-specific plasma markers such as tau proteins ptau181 and ptau217.”

In this five-year study, Church and her co-investigators will explore the relationship between polyphenols, cognitive function, and brain health through four project aims in 50+ year old adults with enhanced risk for Alzheimer’s disease. First, the researchers will assess the protective effects of dietary polyphenol supplementation on brain (using multimodal MRI) and cognitive parameters. Then, they will analyze microbiome metabolites, inflammatory markers, and Alzheimer’s disease biomarkers related to polyphenol intake.

Bioinformatics and machine learning

Afterwards, they will use bioinformatics and machine learning approaches to explore the associations between polyphenol intake and gut microbial metabolites, inflammatory and Alzheimer’s disease markers, brain parameters, and cognitive function. Finally, researchers will use a reverse translational approach whereby stool transplants from high-risk individuals on the polyphenol diet supplementation into mouse models will be conducted to better understand the underlying mechanisms.

“We’re hoping to better understand the role of dietary polyphenols in slowing the development of cognitive decline and how this is all influenced by the brain and gut microbiome,” Church said. “This will help us better understand the ameliorative properties of a polyphenol-rich diet and whether [we need] diet interventions and regimes to delay the onset and progression of cognitive decline.”