Can Improvement of Sleep and Glymphatic Function Reduce the Risk of Developing Alzheimer s Disease-Related Dementia (ADRD) After Traumatic Brain Injury?
Abstract
Alzheimer’s disease-related dementias (ADRD) is a debilitating neurological disorder affecting more than 5 million people in the U.S. and approximately 47 million people worldwide. There is no known treatment to prevent or stop the progression of dementia. Clinical studies suggest that 25%-40% ADRD patients suffer from sleep disturbance. These sleep disturbances precede neuropathology and are augmented by the onset of ß-amyloid and neurofibrillary tau tangles buildup within the brain. Our proposal is based on a novel approach where removal of ß-amyloid from the brain in relevance to sleep and the glymphatic system will be explored. Briefly, the glymphatic system is a glia-dependent brain’s waste product disposal system, which is active during sleep. A compromise of the glymphatic system and sleep is expected in the mouse model of ADRD. Our more recent findings suggest that this removal of waste products from the brain is dependent upon the functioning of lymphatic vessels within the neck region, which drain the head, including the brain. We first plan to explore and define the mechanistic details of this brain-wide clearance pathway and how it is connected to the body’s lymphatic system and then evolve a strategy for how this process could be enhanced. Efficient removal of waste products and metabolites should delay the onset of pathology. It is estimated that any intervention able to delay ADRD symptoms in patients by 5 years would reduce disease burden by 43% by 2050. The experimental outcome is expected to increase our understanding of the glymphatic system, sleep, and other interacting physiological mechanisms and may give us a cue to slow down or delay ADRD.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210676
Entities
People
- Rashad Hussain
Organizations
- United States Army
- University of Rochester