RT Journal Article
SR Electronic
T1 CSF clearance in Alzheimer Disease measured with dynamic PET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP jnumed.116.187211
DO 10.2967/jnumed.116.187211
A1 de Leon, Mony J
A1 Li, Yi
A1 Okamura, Nobuyuki
A1 Tsui, Wai H.
A1 Saint Louis, Les A.
A1 Glodzik, Lidia
A1 Osorio, Ricardo S
A1 Fortea, Juan
A1 Butler, Tracy
A1 Pirraglia, Elizabeth
A1 Fossati, Silvia
A1 Kim, Hee-Jin
A1 Carare, Roxana O.
A1 Nedergaard, Maiken
A1 Benveniste, Helene
A1 Rusinek, Henry
YR 2017
UL http://jnm.snmjournals.org/content/early/2017/03/15/jnumed.116.187211.abstract
AB 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.