Dr Jeffrey IliffJeffrey Iliff, PhD is the Associate Director for Research at the VISN 20 NW Mental Illness Research, Education and Clinical Center (MIRECC) at the VA Puget Sound Health Care System. He is a Professor in the Departments of Psychiatry and Behavioral Sciences and in Neurology at the University of Washington School of Medicine, where he is the Arthur J. and Marcella McCaffray Professor in Alzheimer’s Disease. He also serves as Co-Lead for the UW Alzheimer’s Disease Research Center Research Education Component. Trained in vascular physiology and neuroscience, Dr. Iliff was part of the research team at the University of Rochester Medical Center that between 2012-2014 defined the ‘glymphatic’ system, the brain’s cleaning system that is active during sleep. Beginning in 2014, Dr. Iliff’s research demonstrated that the glymphatic system fails in the aging brain and in the young brain after traumatic brain injury.
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These latter studies suggest that ongoing impairment of the brain’s waste removal system may be the basis for the link between brain trauma (such as concussion) early in life and the development of dementia in the decades that follow. Research in his lab focuses on identifying the molecular changes that underlie glymphatic system failure with aging and after trauma, extending these experimental studies into human subjects and clinical populations with an aim of developing new treatment and prevention strategies for neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
Funding or Dr. Iliff’s work comes from the National Institutes of Health, the University of Washington Departments of Psychiatry and Behavioral Sciences and Department of Neurology, Department of Defense, and the Department of Veterans Affairs.
Funding or Dr. Iliff’s work comes from the National Institutes of Health, the University of Washington Departments of Psychiatry and Behavioral Sciences and Department of Neurology, Department of Defense, and the Department of Veterans Affairs.
Evidence for Sleep-Active Glymphatic Dysfunction in the Pathogenesis of Alzheimer’s Disease
While aging is the strongest risk factor for the development of Alzheimer’s disease, disruption of normal sleep patterns has long been associated with aging and more recently has been associated with the development of Alzheimer’s pathology. Recently, a brain-wide perivascular network termed the ‘glymphatic’ system, has been characterized that facilitates the clearance of interstitial solutes including amyloid beta and tau from the brain. Interestingly, this function was active primarily in the sleeping brain, and is impaired in both the aging and the post-traumatic brain, suggesting one possible basis for the link between aging, sleep disruption and neurodegenerative processes. New data from human clinical subjects suggests that changes in the in elements of the glymphatic system, including the astroglial water channel aquaporin-4 (AQP4) are associated with Alzheimer’s status and pathology, and neurocognitive decline. These findings suggest that glymphatic insufficiency may be one feature of the aging brain that renders it vulnerable to protein mis-aggregation in neurodegenerative conditions such as Alzheimer’s.
