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DYNAMIC CONTRAST-ENHANCED MRI TO ASSESS GLYMPHATIC FUNCTION IN THE NL-F MOUSE MODEL OF ALZHEIMER’S DISEASE

      Understanding the various clearance mechanisms of Aβ and tau from the brain is a vital step towards developing new treatment strategies for Alzheimer’s Disease. The glymphatic system, a fluid network of exchange between cerebrospinal fluid and interstitial fluid, is one pathway through which solutes such as Aβ and tau can be removed, and it’s regulation depends on the water channel aquaporin-4 [Iliff et.al., Sci.Trans.Med.,2012, Iliff et.al.,J.Neurosci.,2014]. We previously demonstrated that pharmacological blockade of aquaporin-4 disrupts glymphatic function and that this can be imaged in real time using DCE-MRI [Harrison et.al.,AAIC,2018]. We also showed that glymphatic function is perturbed in a model of tauopathy and that these changes may be driven by the dysfunction of aquaporin-4 [Harrison et.al.,AAIC,2015]. Here, we investigate changes in glymphatic function during amyloid pathology using the APP NL-F mouse model, which expresses endogenous levels of APP and begins to accumulate pathogenic Aβ from 6 months of age [Saito et.al.,NatNeurosci.,2014].
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