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2019 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

Insulin resistance and inflammation in Alzheimer's: The role of soluble TNF

Can blocking harmful levels of a protein, prevent brain inflammation and insulin problems, which may increase an individual’s Alzheimer’s risk?

Maria Elizabeth De Sousa Rodrigues, Ph.D.
Emory University
Atlanta, GA - United States


Insulin is produced by the body after a meal to help direct the movement of sugar from the bloodstream into cells. Type 2 diabetes is a metabolic disorder where the body’s cells become unable to respond to insulin (meaning they develop insulin resistance). Insulin resistance leads to high blood sugar levels that damage tissues and cause inflammation throughout the body, including the brain. Past studies indicate that people with insulin resistance are at greater risk for developing dementia. Individuals with Alzheimer’s also have inflammation in the brain. Inflammation involves various proteins such as soluble tumor necrosis factor (called solTNF), which are released as part of the body’s response to cell and tissue damage. Increased levels of solTNF have been observed in both people with insulin resistance and in people with neurodegenerative diseases like Alzheimer’s disease. Dr. Maria Elizabeth De Sousa Rodrigues proposes that reducing the levels of solTNF may reduce inflammation, improve sensitivity to insulin, and reduce nerve cell damage in the brain.

Research Plan

Based on preliminary results, Dr. De Sousa Rodrigues has found that blocking solTNF using specific solTNF blockers in genetically engineered Alzheimer’s-like mice decreases the damages caused by inflammation due to high sugar levels, decreases beta-amyloid plaque levels and also corrects the social behavioral problems observed in these mice. To further understand the mechanisms by which metabolic disorder impacts brain inflammation in Alzheimer’s, the researchers will first feed the Alzheimer’s-like mice a high-fat diet, which leads to obesity and the development of insulin resistance. Then the researchers will treat the mice with solTNF blockers and determine the effect on inflammation, insulin resistance, and brain changes related to Alzheimer’s disease.


The study results may help shed light on the complex interplay between metabolic and neurodegenerative diseases, like Alzheimer’s, and how they may be linked to one another. This work may also lead to the development of new anti-inflammatory therapies to slow the progression of neurodegenerative diseases like Alzheimer’s disease.

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