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Does abnormal tau protein lead to insulin resistance in people with Alzheimer’s?
Rabab Al-Lahham
University of Texas
Galveston, TX - United States
Background
People with type 2 diabetes have an increased risk for Alzheimer’s. Diabetes type 2 is a metabolic disorder in which the body’s cells become unable to respond to insulin (meaning, they develop insulin resistance). Insulin signals cells to take in and break down sugarl; thus, insulin resistance leads to dangerously high sugar levels in the blood. It is unclear why Alzheimer’s is linked to insulin resistance and type 2 diabetes.
An early event in Alzheimer’s is the accumulation of an abnormal form of the protein tau, which forms toxic tangles in the brain that interferes with nerve cell function. In a cognitively unimpaired brain, tau has been found to be important for cells to respond to insulin. It is as yet unknown whether abnormal tau in the brains of people with Alzheimer’s leads to insulin resistance.
Research Plan
Dr. Rabab Al-Lahham will study whether in Alzheimer’s, abnormal tau leads to insulin resistance. First, Dr. Al-Lahham will examine whether interfering with normal tau function in mice leads to insulin resistance in liver cells by measuring uptake of sugar to determine if there are differences. The researchers will also use genetically engineered Alzheimer’s-like mice to test whether abnormal tau disrupts a special signaling pathway in the body (known as “p38 MAPK pathway”), which transmits the insulin signal within the liver cell to stimulate sugar metabolism. Finally, she will determine whether treatment of liver cells grown in a laboratory dish with abnormal tau, leads to insulin resistance.
Impact
The study results could help us understand how Alzheimer’s and type 2 diabetes are related and may lead to better methods for identifying individuals who are at increased risk for Alzheimer’s.
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