Subcortical ¹⁸F‐AV‐1451 binding patterns in progressive supranuclear palsy

Abstract

The PSP and PD patients showed distinct subcortical F-AV-1451 binding patterns reflecting subcortical tau pathology in PSP and reduced nigral neuromelanin in PD. However, there was no correlation with the severity of motor dysfunction, no cortical regions with increased binding in PSP patients, and variable degrees of subcortical binding even in the controls. Therefore, the F-AV-1451 PET may be less than ideal for assessing tau pathology in PSP. Further studies will be required to validate the clinical correlation and to understand the clinical utility of F-AV-1451 PET for PSP patients. © 2016 International Parkinson and Movement Disorder Society.

18F‐flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study

“…17 Importantly, off-target binding is detected by autoradiography under some but not all experimental conditions, suggesting that some assays may yield false-negatives in predicting in vivo tracer performance. 17,19 The regionally specific increases in 18 F-flortaucipir uptake that were observed in PSP in our study and others, 11–13 and the correspondence between antemortem tracer retention and postmortem tau pathology in the patient in our study with autopsy-confirmed CBD, are difficult to reconcile with a conclusion that 18 F-flortaucipir has no specific binding to 4-repeat tauopathies. While we cannot rule out the possibility of tracer binding to a process that strongly co-localizes with 4-repeat tau pathology, the absence of elevated uptake in PD patients argues against a more non-specific binding to other misfolded protein aggregates or neurodegenerative markers.…”

“…Elevated uptake in subthalamic nucleus and dorsal midbrain is also a consistent feature, along with the relative absence of tracer retention in pons, cortex and subcortical WM, while uptake in dentate nucleus has been variable. Associations of 18 F-flortaucipir signal with composite measures of disease severity have been inconsistent, 11–13,15 which may be explained by disease heterogeneity in both topographic patterns of binding and clinical progression. Indeed, we identified potential differences in binding patterns between distinct clinical variants of PSP (PSP-PAGF and PSP-CBS compared to PSP-RS) corresponding to reported differences in the distribution of tau pathology across these variants at autopsy, 3 though these findings need to be replicated in larger samples.…”

“…Midbrain binding in healthy older controls may reflect binding to neuromelanin-containing cells in the substantia nigra, 17,19 a finding supported by lower levels of nigral binding in PD in our study and others. 13,39 The cause of off-target binding in other subcortical structures (putamen, pallidum, to a lesser degree thalamus and cerebellum), which correlates with age and is independent of Aβ, is not known. 9,19,33 From a practical point of view, off-target binding may limit the utility of 18 F-flortaucipir in detecting early-stage PSP, in which the distribution and degree of tracer binding will overlap to the greatest degree with binding in controls.…”

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

“…51 Preliminary human PET data suggest binding to areas of known tau pathology in PSP-RS as compared to controls in more advanced patients. 52,53 Several other novel selective tau imaging agents, including 11 C PBB3, have also been reported to bind to PSP tau, but insufficient clinical data exist at this time to gauge their potential utility. 54 …”

Emerging Diagnostic and Therapeutic Strategies for Tauopathies

“…As aforementioned, tau pathology in AD and FTLD-Tau have different biochemical and conformational properties which could contribute. Some studies have shown the ability to discriminate PSPS patients from controls and from patients with AD [26, 75, 76]; however, evidence for potential off-target binding in melanin-containing cells has been described in regions susceptible to PSP tauopathy [74] (i.e., substantia nigra, basal ganglia) which could influence interpretation. Emerging autopsy studies provide good correlation with topography of FTLD-Tau pathology post-mortem and antemortem [ 18 F]AV1451 signal [26, 77], suggesting potential utility in FTLD-Tau but further study with tissue validation for this and other tracers is needed.…”