RT Journal Article
SR Electronic
T1 Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1471
OP 1476
DO 10.2967/jnumed.116.187211
VO 58
IS 9
A1 Mony J. de Leon
A1 Yi Li
A1 Nobuyuki Okamura
A1 Wai H. Tsui
A1 Les A. Saint-Louis
A1 Lidia Glodzik
A1 Ricardo S. Osorio
A1 Juan Fortea
A1 Tracy Butler
A1 Elizabeth Pirraglia
A1 Silvia Fossati
A1 Hee-Jin Kim
A1 Roxana O. Carare
A1 Maiken Nedergaard
A1 Helene Benveniste
A1 Henry Rusinek
YR 2017
UL http://jnm.snmjournals.org/content/58/9/1471.abstract
AB 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.