Title | Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | de Leon MJ, Li Y, Okamura N, Tsui WH, Saint-Louis LA, Glodzik L, Osorio RS, Fortea J, Butler T, Pirraglia E, Fossati S, Kim H-J, Carare RO, Nedergaard M, Benveniste H, Rusinek H |
Journal | J Nucl Med |
Volume | 58 |
Issue | 9 |
Pagination | 1471-1476 |
Date Published | 2017 09 |
ISSN | 1535-5667 |
Keywords | Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Benzothiazoles, Case-Control Studies, Female, Humans, Male, Positron-Emission Tomography, Quinolines, Thiazoles |
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 F-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. Fifteen subjects, 8 with AD and 7 normal control volunteers, were examined with F-THK5117. Ten subjects additionally underwent C-Pittsburgh compound B (C-PiB) PET scanning, and 8 were C-PiB-positive. Ventricular time-activity curves of F-THK5117 were used to identify highly correlated time-activity curves from extracranial voxels. 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. 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. |
DOI | 10.2967/jnumed.116.187211 |
Alternate Journal | J Nucl Med |
PubMed ID | 28302766 |
PubMed Central ID | PMC5577629 |
Grant List | R01 HL111724 / HL / NHLBI NIH HHS / United States R01 NS078167 / NS / NINDS NIH HHS / United States R01 AG048769 / AG / NIA NIH HHS / United States UL1 TR001863 / TR / NCATS NIH HHS / United States R01 AG013616 / AG / NIA NIH HHS / United States R01 NS078304 / NS / NINDS NIH HHS / United States R01 HL118624 / HL / NHLBI NIH HHS / United States P30 AG008051 / AG / NIA NIH HHS / United States R01 AG012101 / AG / NIA NIH HHS / United States R01 NS075177 / NS / NINDS NIH HHS / United States RF1 AG057705 / AG / NIA NIH HHS / United States R21 AG049348 / AG / NIA NIH HHS / United States R01 NS100366 / NS / NINDS NIH HHS / United States T32 AG052909 / AG / NIA NIH HHS / United States |
Related Institute:
Brain Health Imaging Institute (BHII)