Understanding Glymphatic’s Role In Proteinopathies (GRIP): A single centre case-control study protocol
19 affiliations
- 1Department of Neurology, Oslo University Hospital, Oslo, Norway.
- 2Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
- 3The Intervention Centre, Oslo University Hospital, Oslo, Norway.
- 4Department of Physics and Computational Radiology, Oslo University Hospital, Oslo, Norway.
- 5K.G. Jebsen Centre for Brain Fluid Research, Oslo, Norway.
- 6Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
- 7Department of Psychology, Oslo University Hospital, Oslo, Norway.
- 8Department of Pharmacy, University of Oslo, Oslo, Norway.
- 9Department of Transplantation medicine, Oslo University Hospital, Oslo, Norway.
- 10Norwegian Climate and Environmental Research Institute (NILU), Kjeller, Norway.
- 11User representative, Norwegian Health Association, Oslo, Norway.
- 12User representative, Norwegian Parkinson Association, Oslo, Norway.
- 13Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.
- 14Norwegian Health Association, Oslo, Norway.
- 15Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
- 16Department of Neurophysiology, Oslo University Hospital, Oslo, Norway.
- 17Department of Numerical Analysis and Scientific Computing, Simula Research Laboratory, Oslo, Norway.
- 18Department of Mathematics, University of Oslo, Oslo, Norway.
- 19Department of Neurosurgery, Oslo University Hospital, Oslo, Norway.
Abstract
Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia with Lewy bodies (DLB) are proteinopathies characterized by pathological accumulation of amyloid beta, phosphorylated-tau, and alpha-synuclein. Impaired clearance of these proteins is thought to contribute to disease pathogenesis, whereas preserved or enhanced clearance may be compensatory. Beyond intracellular degradation within neurons and glial cells, an extracellular clearance pathway, the glymphatic system, facilitates cerebrospinal fluid flow into perivascular spaces, exchange with interstitial fluid, and subsequent clearance from the brain. Glymphatic transport may therefore be critical for removal of excess proteins and metabolic waste, and its dysfunction could promote protein aggregation and neurodegeneration. The Glymphatic’s Role In Proteinopathies (GRIP) study is an observational case-control imaging and biomarker study comparing glymphatic clearance in patients with AD, PD, and DLB versus healthy controls. We aim to recruit 70 participants: PD (n = 20), DLB (n = 10), AD (n = 20), and age- and sex-matched healthy controls (n = 20). The AD group will be stratified by pathology, with half amyloid-positive/tau-negative (A + T-) and half amyloid- and tau-positive (A + T+). The PD group will be stratified by disease duration. Participants will undergo baseline MRI followed by intrathecal injection of gadobutrol (0.25 mmol) and serial MRI at 5, 24, 48, and 72 hours. Influx and efflux of tracer will be modeled from T1 signal changes. Blood will be sampled repeatedly from 1 to 72 hours; cerebrospinal fluid will be collected at baseline. Individual glymphatic clearance will be estimated using population pharmacokinetic methods, where gadobutrol serves as a tracer. Sleep will be monitored with triaxial accelerometry and sleep diaries. The primary outcome is group differences in glymphatic clearance metrics between each disease group and controls; secondary analyses will explore associations with cognition, disease severity and duration, sleep quality, and cerebrospinal fluid protein levels.
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BibTeX
@article{lian2026understanding,
title = {{Understanding Glymphatic’s Role In Proteinopathies (GRIP): A single centre case-control study protocol}},
author = {Sofie Lysholm Lian and Tryggve Holck Storås and Ebba Müller Gløersen and Grethe Løvland and Einar Hopp and Ingrid Mossige and Markus Hovd and Hilde Thelle Uggerud and Kristin Reimers Kardel and Heidi A Bye and Anne Lise Buset and Kirsten Valdmanis and Anne Brita Knapskog and Anne Rita Øksengård and Tormod Fladby and Kristian Bernhard Nilsen and Kent-André Mardal and Geir Ringstad and Per Kristian Eide and Mathias Toft and Kaja Nordengen},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0360617},
url = {https://doi.org/10.1371/journal.pone.0360617},
note = {CC BY},
}
RIS
TY - JOUR
TI - Understanding Glymphatic’s Role In Proteinopathies (GRIP): A single centre case-control study protocol
AU - Sofie Lysholm Lian
AU - Tryggve Holck Storås
AU - Ebba Müller Gløersen
AU - Grethe Løvland
AU - Einar Hopp
AU - Ingrid Mossige
AU - Markus Hovd
AU - Hilde Thelle Uggerud
AU - Kristin Reimers Kardel
AU - Heidi A Bye
AU - Anne Lise Buset
AU - Kirsten Valdmanis
AU - Anne Brita Knapskog
AU - Anne Rita Øksengård
AU - Tormod Fladby
AU - Kristian Bernhard Nilsen
AU - Kent-André Mardal
AU - Geir Ringstad
AU - Per Kristian Eide
AU - Mathias Toft
AU - Kaja Nordengen
PY - 2026
DA - 2026/10/29
JO - PLOS One
DO - 10.1371/journal.pone.0360617
UR - https://doi.org/10.1371/journal.pone.0360617
AB - Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia with Lewy bodies (DLB) are proteinopathies characterized by pathological accumulation of amyloid beta, phosphorylated-tau, and alpha-synuclein. Impaired clearance of these proteins is thought to contribute to disease pathogenesis, whereas preserved or enhanced clearance may be compensatory. Beyond intracellular degradation within neurons and glial cells, an extracellular clearance pathway, the glymphatic system, facilitates cerebrospinal fluid flow into perivascular spaces, exchange with interstitial fluid, and subsequent clearance from the brain. Glymphatic transport may therefore be critical for removal of excess proteins and metabolic waste, and its dysfunction could promote protein aggregation and neurodegeneration. The Glymphatic’s Role In Proteinopathies (GRIP) study is an observational case-control imaging and biomarker study comparing glymphatic clearance in patients with AD, PD, and DLB versus healthy controls. We aim to recruit 70 participants: PD (n = 20), DLB (n = 10), AD (n = 20), and age- and sex-matched healthy controls (n = 20). The AD group will be stratified by pathology, with half amyloid-positive/tau-negative (A + T-) and half amyloid- and tau-positive (A + T+). The PD group will be stratified by disease duration. Participants will undergo baseline MRI followed by intrathecal injection of gadobutrol (0.25 mmol) and serial MRI at 5, 24, 48, and 72 hours. Influx and efflux of tracer will be modeled from T1 signal changes. Blood will be sampled repeatedly from 1 to 72 hours; cerebrospinal fluid will be collected at baseline. Individual glymphatic clearance will be estimated using population pharmacokinetic methods, where gadobutrol serves as a tracer. Sleep will be monitored with triaxial accelerometry and sleep diaries. The primary outcome is group differences in glymphatic clearance metrics between each disease group and controls; secondary analyses will explore associations with cognition, disease severity and duration, sleep quality, and cerebrospinal fluid protein levels.
SN - 1932-6203
ER -