000007502 001__ 7502
000007502 005__ 20250424233235.0
000007502 0247_ $$2DOI$$a10.6083/6395w780w
000007502 037__ $$aETD
000007502 245__ $$aThe role of AQP4 and the astrocytic endfoot in CSF-ISF exchange and brain waste clearance
000007502 260__ $$bOregon Health and Science University
000007502 269__ $$a2019
000007502 336__ $$aDissertation
000007502 502__ $$bPh.D.
000007502 502__ $$gNeuroscience
000007502 520__ $$aExchange of cerebrospinal fluid (CSF) with interstitial fluid (ISF) is a recently elaborated pathway by which solutes are trafficked into and out of the brain. This pathway has been implicated as a clearance mechanism for proteins such as amyloid β and tau, prior to pathogenic aggregation, a process characteristic of several neurodegenerative diseases. The mechanisms responsible for CSF-ISF exchange are poorly understood but have been linked to the expression of the astrocytic water channel aquaporin-4 (AQP4). AQP4 is unique in that it exhibits a profound localization to the perivascular spaces at which CSF-ISF exchange occurs, and that pathological states, including aging, dramatically reduce this localization. The significance of this loss of localization for CSF-ISF exchange and neurodegenerative disease has not been articulated. Here, we use imaging and cellular based approaches to study the role of AQP4 and the astrocytic endfoot in CSF-ISF exchange and aggregating protein clearance.
000007502 542__ $$fIn copyright - single owner
000007502 650__ $$aalpha-Synuclein$$037032
000007502 650__ $$aAstrocytes$$015172
000007502 650__ $$aGlymphatic System$$012789
000007502 650__ $$aCerebrospinal Fluid$$016377
000007502 650__ $$aAlzheimer Disease$$014513
000007502 650__ $$aAquaporin 4$$036851
000007502 6531_ $$ainterstitial fluid
000007502 691__ $$aSchool of Medicine$$041369
000007502 692__ $$aVollum Institute$$041509
000007502 7001_ $$aSimon, Matthew J.$$uOregon Health and Science University$$041354$$10000-0002-0065-6486
000007502 7201_ $$aIliff, Jeffrey$$uOregon Health and Science University$$041354$$7Personal$$eMentor
000007502 7201_ $$aStork, Philip$$uOregon Health and Science University$$041354$$7Personal$$eCommittee chair
000007502 7201_ $$aUnni, Vivek$$uOregon Health and Science University$$041354$$7Personal$$eCommittee member
000007502 7201_ $$aFreeman, Marc$$uOregon Health and Science University$$041354$$7Personal$$eCommittee member
000007502 7201_ $$aSaugstad, Julie$$uOregon Health and Science University$$041354$$7Personal$$eCommittee member
000007502 8564_ $$96b111dfe-46dc-4d3b-b791-e4a08f1bd29a$$s26419126$$uhttps://digitalcollections.ohsu.edu/record/7502/files/simon.matthew.2019.pdf$$ePublic$$2a7443c1a731a140be01f4c3348004427$$31
000007502 905__ $$a/rest/prod/63/95/w7/80/6395w780w
000007502 909CO $$ooai:digitalcollections.ohsu.edu:7502$$pstudent-work
000007502 980__ $$aTheses and Dissertations