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OtherClinical Investigations (Human)

CSF clearance in Alzheimer Disease measured with dynamic PET

Mony J de Leon, Yi Li, Nobuyuki Okamura, Wai H. Tsui, Les A. Saint Louis, Lidia Glodzik, Ricardo S Osorio, Juan Fortea, Tracy Butler, Elizabeth Pirraglia, Silvia Fossati, Hee-Jin Kim, Roxana O. Carare, Maiken Nedergaard, Helene Benveniste and Henry Rusinek
Journal of Nuclear Medicine March 2017, jnumed.116.187211; DOI: https://doi.org/10.2967/jnumed.116.187211
Mony J de Leon
1 NYU School of Medicine, United States;
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Yi Li
2 NYU Medical center, United States;
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Nobuyuki Okamura
3 Tohoku University School of Medicine, Japan;
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Wai H. Tsui
2 NYU Medical center, United States;
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Les A. Saint Louis
4 Manhattan Diagnostic Radiology, United States;
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Lidia Glodzik
1 NYU School of Medicine, United States;
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Ricardo S Osorio
5 NYU Langone Medical Center, United States;
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Juan Fortea
6 Neurology Service, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Spain;
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Tracy Butler
5 NYU Langone Medical Center, United States;
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Elizabeth Pirraglia
5 NYU Langone Medical Center, United States;
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Silvia Fossati
5 NYU Langone Medical Center, United States;
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Hee-Jin Kim
7 Department of Neurology, Konkuk University College of Medicine, Korea, Republic of;
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Roxana O. Carare
8 Faculty of Medicine, University of Southampton, United Kingdom;
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Maiken Nedergaard
9 9Center for Translational Neuromedicine, University of Rochester Medical Center, United States;
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Helene Benveniste
10 Stony Brook University, United States
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Henry Rusinek
5 NYU Langone Medical Center, United States;
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Abstract

Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer’s disease (AD) comes from primarily from rodent models. However, unlike rodents where predominant extra-cranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Using dynamic Positron Emission Tomography (PET) with 18F‐THK5117 a tracer for tau pathology, the ventricular CSF time activity was used as a biomarker for CSF clearance. We tested three hypotheses: 1. Extra-cranial CSF is detected at the superior turbinates; 2. CSF clearance is reduced in AD; and 3. CSF clearance is inversely associated with amyloid deposition. Methods: 15 subjects, 8 with AD and 7 normal control volunteers were examined with 18F‐THK5117. 10 subjects additionally received 11C-PiB PET scans and 8 were PiB positive. Ventricular time activity curves (TAC) of 18F‐THK5117 were used to identify highly correlated TAC from extra-cranial voxels. Results: For all subjects, the greatest density of CSF positive extra-cranial 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 turbinates 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.

  • Neurology
  • PET/CT
  • Research Methods
  • Alzheimer Disease
  • CSF clearance
  • Dynamic PET
  • THK5117
  • Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
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Journal of Nuclear Medicine: 64 (2)
Journal of Nuclear Medicine
Vol. 64, Issue 2
February 1, 2023
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CSF clearance in Alzheimer Disease measured with dynamic PET
Mony J de Leon, Yi Li, Nobuyuki Okamura, Wai H. Tsui, Les A. Saint Louis, Lidia Glodzik, Ricardo S Osorio, Juan Fortea, Tracy Butler, Elizabeth Pirraglia, Silvia Fossati, Hee-Jin Kim, Roxana O. Carare, Maiken Nedergaard, Helene Benveniste, Henry Rusinek
Journal of Nuclear Medicine Mar 2017, jnumed.116.187211; DOI: 10.2967/jnumed.116.187211

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CSF clearance in Alzheimer Disease measured with dynamic PET
Mony J de Leon, Yi Li, Nobuyuki Okamura, Wai H. Tsui, Les A. Saint Louis, Lidia Glodzik, Ricardo S Osorio, Juan Fortea, Tracy Butler, Elizabeth Pirraglia, Silvia Fossati, Hee-Jin Kim, Roxana O. Carare, Maiken Nedergaard, Helene Benveniste, Henry Rusinek
Journal of Nuclear Medicine Mar 2017, jnumed.116.187211; DOI: 10.2967/jnumed.116.187211
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Cited By...

  • Increased serum peripheral C-reactive protein is associated with reduced small-molecule brain perfusion in healthy volunteers and subjects with major depressive disorder
  • Glymphatic failure as a final common pathway to dementia
  • Dynamic 11C-PiB PET Shows Cerebrospinal Fluid Flow Alterations in Alzheimer Disease and Multiple Sclerosis
  • Dynamic 11C-PiB PET shows cerebrospinal fluid flow alterations in Alzheimers disease and multiple sclerosis
  • Anatomical basis and physiological role of cerebrospinal fluid transport through the murine cribriform plate
  • Reply: Cerebrospinal Fluid, Hyposmia, and Dementia in Alzheimer Disease: Insights from Dynamic PET and a Hypothesis
  • Cerebrospinal Fluid, Hyposmia, and Dementia in Alzheimer Disease: Insights from Dynamic PET and a Hypothesis
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Keywords

  • Neurology
  • PET/CT
  • Research Methods
  • Alzheimer disease
  • CSF clearance
  • dynamic PET
  • THK5117
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