Objective: To test how regional tau pathology and neuroinflammation are associated with clinical severity and survival in progressive supranuclear palsy (PSP).

Background: The abnormal aggregation of tau protein and microglial activation are key etiopathogenetic factors in PSP, as highlighted by in vivo positron emission tomography (PET) and post mortem pathology [1,2].

Method: 17 patients with PSP-Richardson’s syndrome underwent [11C]PK-11195 and [18F]AV-1451 PET imaging, to quantify and localise microglial activation and tau pathology respectively. Clinical severity was longitudinally assessed with the PSP rating scale (PSPRS). Non-displaceable specific binding potential for both PET ligands was calculated in regions of interest including basal ganglia, brainstem, and cerebellum. A temporal ‘staging’ score of disease onset to PET, as a fraction of disease onset to death, was calculated for 14 patients. We tested Pearson correlations between tracer-specific regional values and: (i) baseline estimated PSPRS scores; (ii) temporal stage at the time of PET, and (iii) PSPRS rate of longitudinal change.

Results: PSPRS scores at the time of PET scan positively related to [11C]PK-11195 and [18F]AV-1451 binding in the pallidum, midbrain, and dentate nucleus of the cerebellum (p<0.05) and to [11C]PK-11195 binding in the pons (p=0.003). [11C]PK-11195 binding in pallidum was also positively correlated with temporal PSP stage (0.564, p=0.036). PSPRS rate of longitudinal change negatively correlated with [18F]AV-1451 (-0.550, p=0.027) in the pallidum.

Conclusion: Tau pathology and microglial activation in subcortical regions are related to clinical severity and prognosis in PSP. The negative associations between [18F]AV-1451 PET binding in the pallidum and longitudinal clinical changes can be interpreted in the context of previous imaging and neuropathological studies which have shown severe neuronal loss in the pallidum in PSP.

References: [1] Passamonti, et al. 18F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy. Brain 140.3 (2017): 781-791. [2] Passamonti, et al. [11C] PK11195 binding in Alzheimer disease and progressive supranuclear palsy. Neurology 90.22 (2018): e1989-e1996.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/molecular-correlates-of-survival-and-clinical-severity-in-progressive-supranuclear-palsy/