Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET
Open accessAbstract
Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Dynamic PET with 18F‐THK5117, a tracer for tau pathology, was used to estimate the ventricular CSF time–activity as a biomarker for CSF clearance. We tested 3 hypotheses: extracranial CSF is detected at the superior turbinates; CSF clearance is reduced in AD; and CSF clearance is inversely associated with amyloid deposition. Methods: Fifteen subjects, 8 with AD and 7 normal control volunteers, were examined with 18F‐THK5117. Ten subjects additionally underwent 11C-Pittsburgh compound B (11C-PiB) PET scanning, and 8 were 11C-PiB–positive. Ventricular time–activity curves of 18F‐THK5117 were used to identify highly correlated time–activity curves from extracranial voxels. Results: For all subjects, the greatest density of CSF-positive extracranial voxels was in the nasal turbinates. Tracer concentration analyses validated the superior nasal turbinate CSF signal intensity. AD patients showed ventricular tracer clearance reduced by 23% and 66% fewer superior turbinate CSF egress sites. Ventricular CSF clearance was inversely associated with amyloid deposition. Conclusion: The human nasal turbinate is part of the CSF clearance system. Lateral ventricle and superior nasal turbinate CSF clearance abnormalities are found in AD. Ventricular CSF clearance reductions are associated with increased brain amyloid depositions. These data suggest that PET-measured CSF clearance is a biomarker of potential interest in AD and other neurodegenerative diseases.
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In human subjects, efflux of CSF containing amyloid-β and phospho-tau is reduced in patients with Alzheimer disease compared to age-matched controls.
“in human subjects, efflux of CSF containing amyloid-ß and phosphor-tau is reduced in patients with Alzheimer disease, compared to age-matched controls.”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [70]
The suppression of CSF efflux in Alzheimer disease is substantial enough that it can possibly serve as a biomarker.
“The suppression of CSF in Alzheimer disease is so substantial that it can possible serve as a biomarker (70).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [70]
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- Authors
- de Leon, M. J., Li, Y., Okamura, N., Tsui, W. H., Saint-Louis, L. A., Glodzik, L., Osorio, R. S., Fortea, J., Butler, T., Pirraglia, E., Fossati, S., Kim, H.-J., Carare, R. O., Nedergaard, M., Benveniste, H., & Rusinek, H.
- Affiliations
- NYU Langone Health (US)
- Tohoku University (JP)
- Universitat Autònoma de Barcelona (ES)
- University of Southampton (GB)
- University of Copenhagen (DK)
- Yale University (US)
- ORCID
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2017-03-16
- Volume
- 58
- Issue
- 9
- Pages
- 1471-1476
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- PMC
- PMC5577629
- OpenAlex
- W2595214063
- Cited by
- 246
- References
- 39
- Citations by year
- 2026: 25 · 2025: 34 · 2024: 48 · 2023: 30 · 2022: 30 · 2021: 33 · 2020: 20 · 2019: 11 · 2018: 13 · 2017: 2
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- The Royal Society of Chemistry’s Journals, Books and Databases (The Royal Society of Chemistry) (submittedVersion)
- Funders
- Lundbeckfonden (R155-2016–552)
- Novo Nordisk Fonden (NNF13OC0004258)
- National Institutes of Health (UL1TR001863)
- National Institute on Aging (RF1AG057705, R01AG048769, R01AG012101, R21AG049348, P30AG008051, R01AG013616, T32AG052909)
- National Heart, Lung, and Blood Institute (R01HL118624, R01HL111724)
- National Institute on Drug Abuse
- National Institute of Neurological Disorders and Stroke (R01NS078304, R01NS078167, R01NS075177, R01NS100366)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- cerebrospinal fluid clearance, Alzheimer's disease, tau PET, nasal turbinates, amyloid deposition, [11C]PIB
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Female, Humans, Male, Quinolines, Thiazoles, Case-Control Studies, Positron-Emission Tomography, Benzothiazoles
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