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2016 Grants - Sharma
Role of Circulating MicroRNAs in Alzheimer’s Disease
Salil Sharma, Ph.D.
2016 Alzheimer’s Association Research Fellowship (AARF)
Can a blood-based molecule that regulates gene function serve as a biomarker for the early detection and diagnosis of Alzheimer’s disease?
Small molecules called microRNAs (miRNAs) can affect what genes are turned on/off and therefore can impact many important biological processes. Research suggests that alterations in miRNAs may promote Alzheimer’s disease, but the exact mechanisms remain unclear. In studies using Alzheimer’s-like mice, Salil Sharma, Ph.D., and colleagues found that certain miRNAs present in the blood (known as “circulating” miRNAs) undergo abnormal changes during the earliest stages of disease. They hypothesize that these abnormal miRNAs are able to enter the brain and may promote brain changes associated with Alzheimer’s. In addition, since circulating miRNAs can be collected from the blood, measuring changes in their types or levels may provide a novel tool for early disease detection.
For their current studies, Dr. Sharma and colleagues will analyze over 3,000 different types of circulating miRNAs collected from people with normal cognition and people at various stages of Alzheimer’s disease. They will look for changes in miRNAs that coincide with the onset and progression of Alzheimer’s disease. They will also study miRNAs collected from mice genetically engineered to accumulate tau protein or beta-amyloid in the brain. High brain levels of beta-amyloid (“plaques”) or tau (“tangles’) are hallmarks of Alzheimer’s disease. The researchers will then “cross-reference” the human and mouse studies to identify specific circulating miRNAs that are most related to brain changes associated with Alzheimer’s disease.
The results of these studies could provide new information on the molecular mechanisms of miRNAs in Alzheimer’s disease. Importantly, this work could help determine if circulating miRNAs may serve as blood-based biomarkers for detection and diagnosis of the disease at its earliest stages.