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• W2897547255 abstract "The glymphatic system describes a fluid network of exchange between the cerebrospinal fluid (CSF) and interstitial fluid (ISF), facilitating efficient clearance of solutes and waste from the brain, mediated by water channel aquaporin-4 [Iliff et al., Sci.Trans.Med.,2012]. Waste solutes, such as amyloid-β and tau can depend on the glymphatic clearance for removal [Iliff et.al.,J.Neurosci.,2014]. We showed previously that glymphatic exchange is impaired in a mouse model of tauopathy [Harrison et.al., AAIC,2015] and that disturbances in aquaporin-4, may drive these changes [Ismail et.al.,AAIC,2017]. Here we investigate glymphatic function during the early stages of amyloid-β accumulation in a mouse model of Alzheimer's Disease which accumulates plaque pathology, but with minimal neurodegeneration. Our aim was to investigate the relationship between amyloid-β accumulation and glymphatic clearance. Glymphatic clearance in J20 (PDGF-APPSw, Ind) [Mucke et.al.,J.Neurosci.,2000] (n = 6) and litter-matched wildtype (n = 8) mice at 6 months was captured using contrast-enhanced MRI. Gadolinium was infused intracisternally via a surgically implanted catheter, and its whole brain distribution dynamically imaged using T1-weighted MRI (Fig.1). Histological assessment of astrocytes surrounding blood vessels and quantification of aquaporin-4 expression was also performed. Schematic describing the infusion of gadolinium (Gd-DTPA) into CSF via an indwelling intrathecal cannula, showing time course of imaging experiments and different brain regions analysed. Despite the presence of early amyloid-β pathology in the J20 mice [Mucke et.al.,J.Neurosci.,2000], preliminary data from our investigation showed little change in the quantitative MRI assessment of glymphatic inflow when compared to the wildtype littermates. Histological analysis of aquaporin-4 profiles will investigate the extent to which plaque formation interferes with the expression and polarisation of this channel. These preliminary findings in the J20 mouse suggest that early plaque formation has limited impact on these dynamic MRI measures of glymphatic inflow, in the absence of observable neurodegeneration. Comparison of the current data to quantification of glymphatic function in other mouse models of amyloid pathology (the APP/PS1 mouse [Peng et.al., Nuer B. of Dis.,2016]) suggests that amyloid induced glymphatic changes may differ between genetic strain and harbouring mutations. Together our data suggest that glymphatic impairment during early disease development warrants further investigation." @default.
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• W2897547255 date "2018-07-01" @default.
• W2897547255 modified "2023-10-16" @default.
• W2897547255 title "IC‐P‐052: GLYMPHATIC FUNCTION DURING EARLY STAGE AMYLOID PATHOLOGY: DYNAMIC CONTRAST‐ENHANCED MRI IN THE J20 MOUSE MODEL OF ALZHEIMER'S DISEASE" @default.
• W2897547255 doi "https://doi.org/10.1016/j.jalz.2018.06.2117" @default.
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