Longitudinale Tau-Ablagerung bei nicht-amnestischen Phänotypen der Alzheimer-Krankheit
Nuklearmedizin, Strahlentherapie, Strahlenbiologie
Zusammenfassung der Projektergebnisse
Tau-PET has enabled the visualization of paired helical filaments of 3R/4R tau in Alzheimer’s disease (AD) but its ability to detect aggregated tau in frontotemporal lobar degeneration (FTLD) spectrum disorders is uncertain. We investigated PI-2620, a newer tracer with ex vivo evidence for binding to FTLD-4R-tau, in patients with suspected FTLD-4R-tau and AD using a static acquisition protocol and parametric SUVr images. We analyzed PI-2620-PET data from 65 patients with clinical diagnoses associated with AD or FTLD-4R-tau neuropathology; most (60/65) also had amyloid-PET (Aβ). Scans were acquired 30-60 minutes p.i.; SUVr maps (reference: inferior cerebellar cortex). 23 Aβ-cognitively healthy controls (HC) were enrolled as a control group. Mean SUVr were extracted from globus pallidus, substantia nigra, subthalamic nuclei, dentate nuclei, white matter, and temporal gray matter. Patients with suspected AD neuropathology (Aβ+ patients with mild cognitive impairment or AD dementia) showed high-intensity temporoparietal-predominant PI-2620 binding. At the group level, patients with clinical diagnoses associated with FTLD-4R-tau (progressive supranuclear palsy-Richardson’s syndrome [PSP-RS], corticobasal syndrome, and nonfluent variant primary progressive aphasia) exhibited higher globus pallidus SUVr than HCs; highest pallidal retention was observed in the PSP-RS group, in whom SUVr was correlated with symptom severity (⍴=0.53 p=0.05). At the individual level, only half of patients with suspected FTLD-4R-tau had pallidal SUVr above HC. Temporal SUVr discriminated AD from HC with high accuracy (AUC=0.94 [95%CI: 0.83- 1.00]), whereas discrimination between patients with suspected FTLD-4R-tau and HC using pallidal SUVr was just good 0.73 [95%CI: 59-0.87]. PI-2620 SUVr shows intense and consistent signal in AD, but lower intensity, and heterogenous binding in suspected FTLD-4R- tauopathies. Further work is needed to delineate the substrate of PI-2620 binding and the usefulness of PI2620 SUVr quantification outside of the AD continuum.
