PET Imaging of Neuropathology in Tauopathies: Progressive Supranuclear Palsy

Article type: Research Article

Authors: Kepe, Vladimir^a | Bordelon, Yvette^b | Boxer, Adam^e | Huang, Sung-Cheng^a | Liu, Jie^a | Thiede, Frederick C.^b | Mazziotta, John C.^b | Mendez, Mario F.^{b; c; f} | Donoghue, Natacha^{c; d} | Small, Gary W.^c | Barrio, Jorge R.^{a; *}

Affiliations: [a] Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA | [b] Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA | [c] Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA | [d] Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA | [e] Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA | [f] VA Greater Los Angeles Healthcare Center, Los Angeles, CA, USA

Correspondence: [*] Correspondence to: Jorge R. Barrio, PhD, David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, CHS B2-086A, 694817, 10833 Le Conte Avenue, Los Angeles, CA 90095-6948, USA. Tel.: +1 310 825 4167; Fax: +1 310 825 4517; E-mail: jbarrio@mednet.ucla.edu.

Abstract: 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-Κ 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.

Keywords: FDDNP, neuropathology, Parkinson's disease, positron emission tomography, progressive supranuclear palsy, tauopathy

DOI: 10.3233/JAD-130032

Journal: Journal of Alzheimer's Disease, vol. 36, no. 1, pp. 145-153, 2013