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2022 Alzheimer's Association Research Grant (AARG)

Untangling the Link Between Insulin Resistance and AD through Metabolomics

How may a reduced ability to regulate sugar in the body help promote dementia risk?

Mònica Bulló, Ph.D.
Fundacio Institut d Investigacio Sanitaria Pere Virgili
Tarragona, Spain


Insulin is a hormone that helps the body maintain appropriate levels of blood sugar. Insulin can also be transported to the brain, where it helps maintain nerve cell energy levels and connections between nerve cells. Since insulin plays an important role in the brain, researchers believe insulin may also be associated with Alzheimer’s progression. Past studies have shown that problems with how insulin sends signals in the brain, also known as “insulin resistance”, could be associated with changes in brain cell networks and changes in memory and thinking observed in individuals with Alzheimer’s. As a result, individuals with insulin resistance may be at greater risk for developing dementia.

In previous research with individuals at risk of dementia, Dr. Mònica Bulló and colleagues found that a series of metabolites (compounds produced when the body breaks down sugar into energy) were linked to poor cognitive performance. They also found that a group of fats linked to insulin resistance may promote the accumulation of dementia-related proteins in the brain, such as beta-amyloid plaques and tau tangles, two hallmark brain changes associated with Alzheimer’s.

Research Plan

Dr. Bulló and colleagues will conduct a larger study of insulin resistance and Alzheimer’s using two groups of individuals. The first group will consist of individuals with mild cognitive impairment (or MCI, a condition of subtle memory loss that may precede dementia). Researchers will study the first group by analyzing samples of participant blood and cerebrospinal fluid (or CSF, the biological fluid surrounding the brain and spinal cord), in order to identify specific changes or differences that are linked to insulin resistance and also impact levels of dementia-related proteins in the CSF. Then, over three years, they will assess whether there are differences between the groups. Next, Dr Bulló and team will look for similar measures in their second group of individuals, which will contain individuals with either MCI or no cognitive impairment. For the individuals with MCI, the researchers will identify links between the metabolites and dementia-related proteins. For the individuals with no cognitive impairment, they will look for links between the metabolites and brain changes linked to general aging, such as brain shrinkage.


Results from this project could shed new light on the role of insulin resistance in both dementia and aging. They could also lead to novel methods of diagnosing and treating brain disease.

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