Project Details
Description
PROJECT SUMMARY
Progressive supranuclear palsy (PSP) is a devastating neurodegenerative disorder that is characterized by
deposition of the protein 4-repeat (4R) tau in the brain. Patients typically present with postural instability with
falls, axial rigidity and vertical supranuclear gaze palsy, although other atypical clinical syndromes occur in
which patients present with parkinsonism, freezing of gait, behavioral abnormalities, limb apraxia or speech
and language difficulties. In the 1st cycle of the R01 we characterized the cross-sectional and longitudinal
behavior of the tau-PET ligand [18F]AV-1451 in PSP and showed that it is related to other neuroimaging
measures of neurodegeneration. The 1st cycle focused on the typical clinical presentation of PSP. Since the 1st
cycle, a panel of leading experts published new criteria with a standard to diagnose the atypical clinical
syndromes. We currently lack understanding of the neurobiology of the atypical PSP syndromes. The primary
goal of the 2nd cycle is, therefore, to characterize the clinical, neuroimaging and neuropathological
features across typical and atypical PSP syndromes. Specifically, we aim to characterize the cross-
sectional and longitudinal multi-modal neuroimaging signatures of the PSP syndromes, determine the
relationship between neuroimaging and clinical evolution, and evaluate the autopsy characteristics of the PSP
syndromes. We will have data from 160 PSP patients to allow us to address our aims (84 recruited into the 1st
cycle and 76 which will be recruited in the 2nd cycle). Each newly recruited patient will undergo the identical
examinations as the 84 patients from the 1st cycle, including a neurological and dysphagia evaluation, a 3T
magnetic resonance imaging (MRI) that includes structural MRI and diffusion tensor imaging (DTI), and tau-
PET using the [18F]AV-1451 ligand. All patients will undergo two serial assessments one year apart. We will
assess differences and commonalities in all three neuroimaging modalities across PSP syndromes primarily
using a focused region-of-interest approach which will target key brainstem, subcortical and cortical regions
that are involved in PSP. We will then ascertain whether the PSP syndromes exhibit unique multi-modal
signatures using a classification model. Voxel-level analyses will also be performed to assess patterns across
the whole brain. The relationship between clinical evolution, including the evolution of dysphagia, and the PSP
syndromes and neuroimaging measures will be assessed. Autopsy examinations will be performed on all
patients from both cycles that die and 4R tau burden will be compared across PSP syndromes. We will also
determine the degree to which neuroimaging differences across syndromes are related to tau burden and
investigate how additional pathologies are associated with the different syndromes. The results of this grant will
increase our knowledge of the neural underpinnings of the clinical and anatomical heterogeneity in PSP and
will also be essential for the development of optimum biomarkers for PSP that will aid diagnosis, track disease
progression and allow patients with all PSP syndromes to be included in future treatment trials.
Status | Active |
---|---|
Effective start/end date | 9/15/15 → 8/31/24 |
Funding
- National Institute of Neurological Disorders and Stroke: $324,775.00
- National Institute of Neurological Disorders and Stroke: $331,518.00
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.