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J Cereb Blood Flow Metab. 2019 Sep 7:271678X19874790. doi: 10.1177/0271678X19874790. [Epub ahead of print]

Delayed clearance of cerebrospinal fluid tracer from choroid plexus in idiopathic normal pressure hydrocephalus.

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Department of Neurosurgery, Oslo University Hospital - Rikshospitalet, Oslo, Norway.
Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Mathematics, University of Oslo, Oslo, Norway.
Oslo Centre of Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway.
Center for Biomedical Computing, Simula Research Laboratory, Lysaker, Norway.
Division of Radiology and Nuclear Medicine, Department of Radiology, Oslo University Hospital - Rikshospitalet, Oslo, Norway.


Impaired clearance of amyloid-β from choroid plexus is one proposed mechanism behind amyloid deposition in Alzheimer's disease. The present study examined whether clearance from choroid plexus of a cerebrospinal fluid tracer, serving as a surrogate marker of a metabolic waste product, is altered in idiopathic normal pressure hydrocephalus (iNPH), one sub-type of dementia. In a prospective observational study of close to healthy individuals (reference cohort; REF) and individuals with iNPH, we performed standardized T1-weighted magnetic resonance imaging scans before and through 24 h after intrathecal administration of a cerebrospinal fluid tracer (the magnetic resonance imaging contrast agent gadobutrol). Changes in normalized T1 signal within the choroid plexus and cerebrospinal fluid of lateral ventricles were quantified using FreeSurfer. The normalized T1 signal increased to maximum within choroid plexus and cerebrospinal fluid of lateral ventricles 6-9 h after intrathecal gadobutrol in both the REF and iNPH cohorts (enrichment phase). Peak difference in normalized T1 signals between REF and iNPH individuals occurred after 24 h (clearance phase). The results gave evidence for gadobutrol resorption from cerebrospinal fluid by choroid plexus, but with delay in iNPH patients. Whether choroid plexus has a role in iNPH pathogenesis in terms of delayed clearance of amyloid-β remains to be shown.


CSF tracer; Idiopathic normal pressure hydrocephalus; cerebrospinal fluid; choroid plexus; clearance; glymphatic; humans; intrathecal contrast agents; magnetic resonance imaging


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