Weill Cornell Medicine
Dept Radiology,
Mony J. de Leon Is Professor of Neuroscience in Radiology at Weill Cornell Medicine. For over 40 years, he and his teams have developed diagnostic imaging tests for Alzheimer's disease (AD) and related disorders. Highlighted among their scientific achievements are: the first imaging evidence, using CT, for excess cortical atrophy in dementia (1979); the first report of glucose metabolism reductions in AD using FDG-PET (1980); a 30 year longitudinal study with post-mortem validations of hippocampal formation pathology using CT, PET, and MRI that contributed to the AD diagnosis and to understandings of the predictive value of structural and metabolic imaging in aging, MCI, and AD (1989-2019); and currently, the use of novel dynamic PET tracers to identify CSF clearance pathways and test hypotheses related to impaired CSF drainage and misfolded protein accumulations in the aging human brain (2017, 2022). Dr. de Leon has received several life-time achievement awards and international honors and his colleagues and students have received many awards and acknowledgements for their scientific contributions.

Moderator of 1 Session

Session Time
08:40 - 10:40
Session Type
SYMPOSIUM
Date
Sat, 01.04.2023
Room
ONSITE - HALL G3

Presenter of 1 Presentation

CSF DRAINAGE PATHWAYS ARE REDUCED IN NORMAL AGING USING PET WITH [11C]-BUTANOL AND ASSOCIATED WITH BRAIN AMYLOID

Session Type
SYMPOSIUM
Date
Sat, 01.04.2023
Session Time
08:40 - 10:40
Room
ONSITE - HALL G3
Lecture Time
09:10 - 09:25

Abstract

Aims

CSF production and drainage are vital brain functions with deficiencies contributing to amyloid lesions in murine models of aging and Alzheimer’s disease (AD). We developed a human PET based technology to measure CSF drainage (de Leon et al 2017). Using [18F]-tau tracers we replicated our findings of reduced ventricular CSF drainage in AD and the association with [11C]-PiB PET amyloid accumulation (Li et al 2022). We recently developed an improved PET radiotracer for CSF dynamics [11C]-Butanol, a highly permeable alcohol that does not bind to brain tissues. [11C]-Butanol with a 20min half-life enables unbiased estimates of brain CSF egress. We hypothesized that CSF turnover is reduced in normal elders, associated with amyloid, and that anatomical CSF egress pathways could be identified.

Methods

Thirty-two normal subjects between the ages of 20-85y were examined. Dynamic list mode [11C]-Butanol PET, [18F]MK6240, and [11C]-PiB were sequentially obtained and co-registered to MRI. Tracer time activity data were used to model the egress of CSF from brain and extra-cranial sites. We examined known CSF draining regions including: brain, ventricle, nasal turbinates, superior sagittal sinus, optic nerve sheath, and control regions.

Results

Ventricular [11C]-Butanol production and clearance reductions are age associated (r=-.83, p<.01) and reduced in subjects above the median age of 67y (~23%, p<.05). Ventricular CSF egress reductions are associated with global brain amyloid (p<.05), but not global brain tau estimates. Using [11C]-Butanol we identified the optic nerve sheath as a CSF egress site affected by aging.

Conclusions

PET imaging of CSF may provide quantitative evidence for drainage pathways carrying misfolded proteins impacted by age.

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