PT  - JOURNAL ARTICLE
AU  - Mony J de Leon
AU  - Yi Li
AU  - Nobuyuki Okamura
AU  - Wai H. Tsui
AU  - Les A. Saint Louis
AU  - Lidia Glodzik
AU  - Ricardo S Osorio
AU  - Juan Fortea
AU  - Tracy Butler
AU  - Elizabeth Pirraglia
AU  - Silvia Fossati
AU  - Hee-Jin Kim
AU  - Roxana O. Carare
AU  - Maiken Nedergaard
AU  - Helene Benveniste
AU  - Henry Rusinek
TI  - CSF clearance in Alzheimer Disease measured with dynamic PET
AID  - 10.2967/jnumed.116.187211
DP  - 2017 Mar 01
TA  - Journal of Nuclear Medicine
PG  - jnumed.116.187211
4099  - http://jnm.snmjournals.org/content/early/2017/03/15/jnumed.116.187211.short
4100  - http://jnm.snmjournals.org/content/early/2017/03/15/jnumed.116.187211.full
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.