Role of Obesity and Glucose Homeostasis in the Regulation of Brain Perineuronal Net Reorganization in Alzheimer s Disease
Abstract
Alzheimer’s disease (AD) associates with a decrease in important brain matrix structures that surround and protect neurons involved in cognition and memory. We discovered that in addition to the loss of the abundance of these important matrix structures, patients with AD also exhibit changes in the chemical composition of these brain matrices that appear to increase interaction with a pathological protein, termed Tau. Here, we address the Convergence Science Research Award (CSRA) Dementia Category Alzheimer’s Dementia by proposing to test whether the CRSA Military Risk Factor of Metabolic Impairments influences either the abundance or the composition of these protective matrices in a mouse model of pathological Tau. We predict that obesity and type 2 diabetes (T2D) will increase binding interactions between the brain matrices and the pathological Tau protein that will result in its accumulation in the Tau mice. In addition, we also want to determine if current drug therapies that stabilize brain matrix structures can prevent, or even reverse, the pathological accumulation of Tau in our mouse model. We predict that by fixing the defects in either the abundance or composition of these unique brain matrix structures, we can prevent the accumulation of pathological Tau in the brain and translate these findings for future treatments of AD. Such a result will impact future clinical drug development targeting matrix stabilization for the prevention and reversal AD.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210603
Entities
People
- Kimberly M Alonge
Organizations
- United States Army
- University of Washington