More Evidence for Gut-Brain Link in Alzheimer's Disease

Megan Brooks

July 30, 2018

CHICAGO — New research provides more evidence that the gut microbiome may play a role in the etiology of Alzheimer's disease (AD).

The study found an association between changes in gut microbiome–produced bile acids and AD-related structural and functional neuroimaging biomarkers, as well as cerebrospinal fluid (CSF) biomarkers of amyloid-β and tau.

The findings provide "further support for a role of bile acid pathways in Alzheimer's disease," said lead investigator Kwangsik Nho, PhD, from the Center for Neuroimaging at Indiana University School of Medicine in Indianapolis.

"Bile acid signaling pathways may lead to the identification of metabolites that are protective against Alzheimer's and could foster novel therapeutic strategies, if a causal role can be demonstrated in future studies," Nho said at a press briefing devoted to gut-liver-brain axis research here at the Alzheimer's Association International Conference (AAIC) 2018.

"New therapies based on modulation of gut microbiome with drugs or probiotics could emerge as new approaches to the treatment of AD," he added.

Gut Health Linked to Brain Health

In an attempt to connect peripheral metabolic changes and brain changes in AD, Nho and colleagues analyzed data on 1562 older adults with early-stage AD or who were at risk for AD from the Alzheimer's Disease Neuroimaging Initiative cohort.

They assessed the association of bile acids with CSF biomarkers and neuroimaging biomarkers, including brain atrophy measured by MRI and brain glucose metabolism measured by fluorodeoxyglucose positron emission tomography.

Nho said three key findings emerged.

First, lower serum concentrations of primary bile acids synthesized in the liver from cholesterol were significantly associated with worse cognitive function, decreased hippocampal volume, and decreased brain glucose metabolism.

Second, higher serum concentrations of secondary bile acids produced in the gut by bacteria were significantly associated with higher CSF phosphorylated tau and CSF total tau levels, as well as larger brain structural atrophy and decreased brain glucose metabolism.

Third, higher serum concentrations of ratios of bacterially produced secondary bile acids to primary bile acids were significantly associated with lower CSF Aβ1-42 values, larger brain structural atrophy, and decreased brain glucose metabolism.

A New Frontier

"While still in its infancy, gut microbiome research is very exciting since it may give us a new window into why diet and nutrition are so important for brain health," Maria Carrillo, PhD, Alzheimer's Association chief science officer, said in a conference statement. "For example, this work may tell us more about how and why 'good fats' help keep the brain healthy, and help guide brain-healthy dietary choices."

"In addition," said Carrillo, "if it turns out these gut bacteria are effective and accurate markers of Alzheimer's disease cause or progression, or both, they might be useful as a noninvasive screening tool — a simple blood test. They could then be used to help identify high-risk people for clinical trials or track the impact of a therapy. However, we are only at step one. We don't know yet exactly what the changes we are seeing mean — especially in animal models — whether they are cause or effect."

Briefing moderator Martha Clare Morris, ScD, from Rush University, Chicago, Illinois, said investigations into the gut-brain axis as it relates to AD is a "new frontier in science" that may lead to new discoveries in the prevention and treatment of AD.

"The last 15 years of research has established diet as an important risk factor in the development of Alzheimer's disease. This new field of research is uncovering how eating patterns may be related to brain health and dementia," said Morris.

She noted that the Alzheimer's Association has taken a "major step" in advancing this science by funding the US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (US POINTER), which will test whether a combined treatment of a healthy diet, exercise, cognitive and social stimulation, and management of cardiovascular conditions will prevent decline in cognitive abilities and the development of AD.    

The study was funded by the US National Institute on Aging and the National Library of Medicine. The authors have disclosed no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2018. Abstract 26438. Presented July 24, 2018.

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