Cerebrospinal fluid clearance in Alzheimer disease measured with dynamic PET
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Cerebrospinal fluid clearance in Alzheimer disease measured with dynamic PET. / De Leon, Mony J.; Li, Yi; Okamura, Nobuyuki; Tsui, Wai H.; Saint-Louis, Les A.; Glodzik, Lidia; Osorio, Ricardo S.; Fortea, Juan; Butler, Tracy; Pirraglia, Elizabeth; Fossati, Silvia; Kim, Hee Jin; Carare, Roxana O.; Nedergaard, Maiken; Benveniste, Helene; Rusinek, Henry.
In: Journal of Nuclear Medicine, Vol. 58, No. 9, 2017, p. 1471-1476.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cerebrospinal fluid clearance in Alzheimer disease measured with dynamic PET
AU - De Leon, Mony J.
AU - Li, Yi
AU - Okamura, Nobuyuki
AU - Tsui, Wai H.
AU - Saint-Louis, Les A.
AU - Glodzik, Lidia
AU - Osorio, Ricardo S.
AU - Fortea, Juan
AU - Butler, Tracy
AU - Pirraglia, Elizabeth
AU - Fossati, Silvia
AU - Kim, Hee Jin
AU - Carare, Roxana O.
AU - Nedergaard, Maiken
AU - Benveniste, Helene
AU - Rusinek, Henry
PY - 2017
Y1 - 2017
N2 - 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.
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.
KW - Alzheimer disease
KW - CSF clearance
KW - Dynamic PET
KW - Neurology
KW - PET/CT
KW - Research methods
KW - THK5117
U2 - 10.2967/jnumed.116.187211
DO - 10.2967/jnumed.116.187211
M3 - Journal article
C2 - 28302766
AN - SCOPUS:85028021300
VL - 58
SP - 1471
EP - 1476
JO - The Journal of Nuclear Medicine
JF - The Journal of Nuclear Medicine
SN - 0161-5505
IS - 9
ER -
ID: 184296551