E1452. Glymphatic System Dysfunction, Enlarged Perivascular Spaces and Neurodegeneration: Components of the Same Spectrum
  1. Nathan Gruenhagen; Froedtert Hospital; Medical College of Wisconsin
  2. Eashna Agarwal; Medical College of Wisconsin
  3. Yang Wang; Froedtert Hospital; Medical College of Wisconsin
  4. Malgorzata Franczak; Froedtert Hospital; Medical College of Wisconsin
  5. Andrew Klein; Froedtert Hospital; Medical College of Wisconsin
The glymphatic system (GS) is a recently described system of CSF and interstitial fluid (ISF) exchange which has been proposed to be the major pathway of CSF circulation. Understanding the pathophysiology of the GS will play a key role in understanding disease processes including neurodegenerative conditions and traumatic brain injury. The GS may play a role in future imaging techniques.

Educational Goals / Teaching Points
1. The perivascular spaces (PVS) serve as the central routes for CSF circulation into the brain parenchyma and the CSF-ISF exchange are an important component of the GS. 2. There is mounting evidence that the GS has a role in brain waste clearance. 3. GS dysfunction in old age, cerebrovascular disease (CVD), neurodegenerative conditions, and traumatic brain injury (TBI) leads to impaired clearance of proteins such as amyloid beta, tau etc. 4. Enlarged PVS may be seen in physiological and pathological conditions like old age, CVD, TBI and dementia which may be a manifestation of GS dysfunction. 5. GS is most active during sleep and sleep disturbances may be associated with GS dysfunction.

Key Anatomic/Physiologic Issues and Imaging Findings/Techniques
1. CSF production and circulation. a. Blood-brain barrier and blood-CSF barrier physiology. b. CSF-ISF exchange. 2. GS physiology. a. Diagrammatic approach to understanding CSF and ISF pathways along PVS and interstitial spaces. b. Role in waste removal and solute distribution with focus on lipid distribution, tau protein clearance, and beta amyloid clearance. c. Proposed mechanisms that relate GS dysfunction with neurodegenerative disease, CVD, TBI and aging. d. How sleep and norepinephrine affect GS clearance. 3. GS Imaging a. In vivo two-photon imaging in mouse models. b. Novel MRI phantom prototype to quantitate glymphatic flow.

Understanding the physiology of the GS will aid in understanding research surrounding pathologies including cerebrovascular disease, neurodegenerative conditions, and traumatic brain injury. New cutting-edge imaging techniques utilize the GS and may play a key role in future evaluation of these disease processes.