{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, Oslo University Hospital, Oslo, Norway.",
    "Institute of Clinical Medicine, University of Oslo, Oslo, Norway.",
    "The Intervention Centre, Oslo University Hospital, Oslo, Norway.",
    "Department of Physics and Computational Radiology, Oslo University Hospital, Oslo, Norway.",
    "K.G. Jebsen Centre for Brain Fluid Research, Oslo, Norway.",
    "Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.",
    "Department of Psychology, Oslo University Hospital, Oslo, Norway.",
    "Department of Pharmacy, University of Oslo, Oslo, Norway.",
    "Department of Transplantation medicine, Oslo University Hospital, Oslo, Norway.",
    "Norwegian Climate and Environmental Research Institute (NILU), Kjeller, Norway.",
    "User representative, Norwegian Health Association, Oslo, Norway.",
    "User representative, Norwegian Parkinson Association, Oslo, Norway.",
    "Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.",
    "Norwegian Health Association, Oslo, Norway.",
    "Department of Neurology, Akershus University Hospital, Lørenskog, Norway.",
    "Department of Neurophysiology, Oslo University Hospital, Oslo, Norway.",
    "Department of Numerical Analysis and Scientific Computing, Simula Research Laboratory, Oslo, Norway.",
    "Department of Mathematics, University of Oslo, Oslo, Norway.",
    "Department of Neurosurgery, Oslo University Hospital, Oslo, Norway."
  ],
  "article_type": "Study Protocol",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sofie Lysholm Lian"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Tryggve Holck Storås"
    },
    {
      "affs": [
        5
      ],
      "name": "Ebba Müller Gløersen"
    },
    {
      "affs": [
        2
      ],
      "name": "Grethe Løvland"
    },
    {
      "affs": [
        2,
        3,
        6
      ],
      "name": "Einar Hopp",
      "orcid": "0000-0003-3905-2986"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Ingrid Mossige",
      "orcid": "0009-0009-3342-8592"
    },
    {
      "affs": [
        4,
        7,
        8
      ],
      "name": "Markus Hovd",
      "orcid": "0000-0002-6077-0934"
    },
    {
      "affs": [
        9
      ],
      "name": "Hilde Thelle Uggerud"
    },
    {
      "affs": [
        10
      ],
      "name": "Kristin Reimers Kardel"
    },
    {
      "affs": [
        11
      ],
      "name": "Heidi A Bye"
    },
    {
      "affs": [
        11
      ],
      "name": "Anne Lise Buset"
    },
    {
      "affs": [
        11
      ],
      "name": "Kirsten Valdmanis"
    },
    {
      "affs": [
        1,
        12
      ],
      "name": "Anne Brita Knapskog"
    },
    {
      "affs": [
        13
      ],
      "name": "Anne Rita Øksengård",
      "orcid": "0000-0003-4946-1249"
    },
    {
      "affs": [
        1,
        14
      ],
      "name": "Tormod Fladby"
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    {
      "affs": [
        1,
        15
      ],
      "name": "Kristian Bernhard Nilsen"
    },
    {
      "affs": [
        4,
        16,
        17
      ],
      "name": "Kent-André Mardal"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Geir Ringstad"
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    {
      "affs": [
        1,
        4,
        18
      ],
      "name": "Per Kristian Eide"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mathias Toft"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "Kaja Nordengen",
      "orcid": "0000-0002-5897-6394"
    }
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  "licence_label": "CC BY",
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  "native_subjects": [
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  "pmcid": "PMC13718934",
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  "published": "2026-10-29",
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "heading:Biochemistry",
      "subfield": "general"
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    {
      "field": "medicine",
      "origin": "plos:diagnostic radiology",
      "subfield": "imaging"
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    {
      "field": "medicine",
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    {
      "field": "medicine",
      "origin": "heading:Mental Health and Psychiatry",
      "subfield": "psychiatry"
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  "title": "Understanding Glymphatic’s Role In Proteinopathies (GRIP): A single centre case-control study protocol",
  "title_text": "Understanding Glymphatic’s Role In Proteinopathies (GRIP): A single centre case-control study protocol",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:52Z",
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