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2017 Grants - Cattaneo
Gut Microbiota and Host Epigenome Interplay in Alzheimer's Disease
Annamaria Cattaneo, Ph.D.
Scientific Institute Saint John of God - The National Centre for Research and Care of Alzheimer's and Mental Diseases
2017 Alzheimer’s Association Research Grant (AARG)
Can bacteria in the gut or other fluids alter one’s risk for Alzheimer’s?
Recent studies have found that Alzheimer’s disease may be linked to problems with the innate immune system, the part of the immune system that responds in a general way to foreign substances. Damage to this system may, for example, hinder the body from clearing harmful beta-amyloid, a protein fragment linked to Alzheimer’s-related brain cell damage and death. However, the exact mechanisms that link immune system damage and Alzheimer’s risk remain unclear.
One biological factor that influences the innate immune system is the gut microbiota, or the composition of bacteria and other microscopic substances in the gastrointestinal tract. In preliminary research, Annamaria Cattaneo, Ph.D., and colleagues found that mice engineered to develop Alzheimer’s-like brain changes had a different composition of gut microbiota than did healthy mice. They also observed similar differences between people with Alzheimer’s disease and healthy individuals. These findings suggest a mechanism for how the immune system may promote the development of Alzheimer’s.
For their research grant, the investigators will conduct a larger study to confirm and expand on their earlier work. They will use several methods to assess the gut microbiota in human participants with Alzheimer’s disease. First, they will analyze bacterial composition in the participants’ stools. Then, because some gut bacteria can circulate throughout the body, the researchers will measure bacterial composition in the participants’ blood and cerebrospinal fluid (or fluid surrounding the brain). They will also determine whether fluid bacteria may promote inflammation, a common hallmark of Alzheimer’s disease. Lastly, the team will assess whether changes in gut microbiota may promote alterations to the participants’ epigenome — or the record of chemical modifications that turn genes “on” or “off”. Such modifications may become altered in ways that contribute to Alzheimer’s progression.
The results of this study could identify bacterial changes as an important indicator of Alzheimer’s disease risk. In addition, therapies for altering microbiota composition (including diet and other lifestyle changes) could potentially be used to help reduce or prevent dementia onset.