Palleis, Carla and Franzmeier, Nicolai and Weidinger, Endy and Bernhardt, Alexander M. and Katzdobler, Sabrina and Wall, Stephan and Ferschmann, Christian and Harris, Stefanie and Schmitt, Julia and Schuster, Sebastian and Gnoerich, Johannes and Finze, Anika and Biechele, Gloria and Lindner, Simon and Albert, Nathalie L. and Bartenstein, Peter and Sabri, Osama and Barthel, Henryk and Rupprecht, Rainer and Nuscher, Brigitte and Stephens, Andrew W. and Rauchmann, Boris-Stephan and Perneczky, Robert and Haass, Christian and Brendel, Matthias and Levin, Johannes and Hoeglinger, Guenter U. (2024) Association of Neurofilament Light Chain, [¹⁸F]PI-2620 Tau-PET, TSPO-PET, and Clinical Progression in Patients With β-Amyloid-Negative CBS. NEUROLOGY, 102 (1): e207901. ISSN 0028-3878, 1526-632X
Full text not available from this repository. (Request a copy)Abstract
Background and ObjectivesCorticobasal syndrome (CBS) with underlying 4-repeat tauopathy is a progressive neurodegenerative disease characterized by declining cognitive and motor functions. Biomarkers for assessing pathologic brain changes in CBS including tau-PET, 18 kDa translocator protein (TSPO)-PET, structural MRI, neurofilament light chain (NfL), or glial fibrillary acidic protein (GFAP) have recently been evaluated for differential diagnosis and disease staging, yet their association with disease trajectories remains unclear. Therefore, we performed a head-to-head comparison of neuroimaging (tau-PET, TSPO-PET, structural MRI) and plasma biomarkers (NfL, GFAP) as prognostic tools for longitudinal clinical trajectories in beta-amyloid (A beta)-negative CBS.MethodsWe included patients with clinically diagnosed A beta-negative CBS with clinical follow-up data who underwent baseline structural MRI and plasma-NfL analysis for assessing neurodegeneration, [F-18]PI-2620-PET for assessing tau pathology, [F-18]GE-180-PET for assessing microglia activation, and plasma-GFAP analysis for assessing astrocytosis. To quantify tau and microglia load, we assessed summary scores of whole-brain, cortical, and subcortical PET signal. For structural MRI analysis, we quantified subcortical and cortical gray matter volume. Plasma NfL and GFAP values were assessed using Simoa-based immunoassays. Symptom progression was determined using a battery of cognitive and motor tests (i.e., Progressive Supranuclear Palsy Rating Scale [PSPRS]). Using linear mixed models, we tested whether the assessed biomarkers at baseline were associated with faster symptom progression over time (i.e., time x biomarker interaction).ResultsOverall, 21 patients with A beta-negative CBS with similar to 2-year clinical follow-up data were included. Patients with CBS with more widespread global tau-PET signal showed faster clinical progression (PSPRS: B/SE = 0.001/0.0005, p = 0.025), driven by cortical rather than subcortical tau-PET. By contrast, patients with higher global [F-18]GE-180-PET readouts showed slower clinical progression (PSPRS: B/SE = -0.056/0.023, p = 0.019). No association was found between gray matter volume and clinical progression. Concerning fluid biomarkers, only higher plasma-NfL (PSPRS: B/SE = 0.176/0.046, p < 0.001) but not GFAP was associated with faster clinical deterioration. In a subsequent sensitivity analysis, we found that tau-PET, TSPO-PET, and plasma-NfL showed significant interaction effects with time on clinical trajectories when tested in the same model.Discussion[F-18]PI-2620 tau-PET, [F-18]GE-180 TSPO-PET, and plasma-NfL show prognostic potential for clinical progression in patients with A beta-negative CBS with probable 4-repeat tauopathy, which can be useful for clinical decision-making and stratifying patients in clinical trials.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FIBRILLARY ACIDIC PROTEIN; MICROGLIAL ACTIVATION; DISEASE; DIAGNOSIS; BIOMARKER; BINDING; SCALE |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Jan 2026 09:47 |
| Last Modified: | 27 Jan 2026 09:47 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65360 |
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