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J Nucl Med. 2017 Sep;58(9):1471-1476. doi: 10.2967/jnumed.116.187211. Epub 2017 Mar 16.

Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET.

Author information

1
Department of Psychiatry, New York University School of Medicine, Center for Brain Health, New York, New York mony.deleon@nyumc.org.
2
Department of Psychiatry, New York University School of Medicine, Center for Brain Health, New York, New York.
3
Department of Pharmacology, Tohoku University School of Medicine, Tohoku, Japan.
4
Manhattan Diagnostic Radiology, New York, New York.
5
Department of Radiology, New York University Center School of Medicine, New York, New York.
6
Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
7
Department of Neurology, New York University School of Medicine, New York, New York.
8
Department of Neurology, College of Medicine, Hanyang University, Seoul, Korea.
9
Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
10
Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York.
11
Center for Basic and Translational Neuroscience, University of Copenhagen, Copenhagen, Denmark; and.
12
Department of Anesthesiology, Yale School of Medicine, New Haven, Connecticut.

Abstract

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.

KEYWORDS:

Alzheimer disease; CSF clearance; PET/CT; THK5117; dynamic PET; neurology; research methods

PMID:
28302766
PMCID:
PMC5577629
DOI:
10.2967/jnumed.116.187211
[Indexed for MEDLINE]
Free PMC Article

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