PET Imaging of Neuropathology in Tauopathies: Progressive Supranuclear Palsy
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OBJECTIVE: Currently [18F]FDDNP is the only PET imaging probe with the ability to visualize hyperphosphorylated tau fibrillar aggregates in living subjects. In this work, we evaluate in vivo [18F]FDDNP labeling of brain neuropathology, primarily tau fibrillar aggregates, in patients with progressive supranuclear palsy (PSP), a human tauopathy usually lacking amyloid-β deposits. METHODS: Fifteen patients with PSP received [18F]FDDNP PET scanning. [18F]FDDNP distribution volume ratios, in reference to cerebellar gray matter, were determined for cortical and subcortical areas and compared with those of patients with Parkinson's disease with short disease duration, and age-matched control subjects without neurodegenerative disorders. RESULTS: [18F]FDDNP binding was present in subcortical areas (e.g., striatum, thalamus, subthalamic region, midbrain, and cerebellar white matter) regardless of disease severity, with progressive subcortical and cortical involvement as disease severity increased. Brain patterns of [18F]FDDNP binding were entirely consistent with the known pathology distribution for PSP. High midbrain and subthalamic region [18F]FDDNP binding was distinctive for PSP subjects and separated them from controls and patients with Parkinson's disease. CONCLUSIONS: These results provide evidence that [18F]FDDNP is a sensitive in vivo PET imaging probe to map and quantify the dynamic regional localization of tau fibrillar aggregates in PSP. Furthermore, [18F]FDDNP PET may provide a tool to detect changes in tau pathology distribution either associated with disease progression or as a treatment biomarker for future tau-specific therapies. Patterns of [18F]FDDNP binding may also be useful in diagnosis early in disease presentation when clinical distinction among neurodegenerative disorders is often difficult.
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Earlier PET investigations have detected alterations in PSP with ligands for tau and for microglial activation.
“Previous positron emission tomography (PET) has indicated changes in PSP using ligands targeting tau8–16 and microglial activation17,18.”
From Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy (2020) · cites this paper as [11]
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- Authors
- Kepe, V., Bordelon, Y., Boxer, A., Huang, S.-C., Liu, J., Thiede, F. C., Mazziotta, J. C., Mendez, M. F., Donoghue, N., Small, G. W., & Barrio, J. R.
- Affiliations
- University of California, Los Angeles (US)
- University of California, San Francisco (US)
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2013-06-04
- Volume
- 36
- Issue
- 1
- Pages
- 145-153
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC3674205
- OpenAlex
- W1538352135
- Cited by
- 106
- References
- 36
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 6 · 2022: 5 · 2021: 8 · 2020: 8 · 2019: 6 · 2018: 11 · 2017: 12 · 2016: 16 · 2015: 15 · 2014: 12 · 2013: 3
- FWCI
- 10.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Aging (P01AG025831, P50AG016570, R01AG034499, R01AG031278, R01AG038791)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- progressive supranuclear palsy
- MeSH terms
- Aged, Aged, 80 and over, Brain, Cerebellum, Corpus Striatum, Female, Humans, Male, Mesencephalon, Middle Aged, Nitriles, Parkinson Disease, Supranuclear Palsy, Progressive, Thalamus, Disease Progression, Positron-Emission Tomography, Neuroimaging
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