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Updated: Jun 17, 2026
A Technique for Serial Collection of Cerebrospinal Fluid from the Cisterna Magna in Mouse
Published on: November 10, 2008
Association of Neurofilament Light Chain, [18F]PI-2620 Tau-PET, TSPO-PET, and Clinical Progression in Patients With
Carla Palleis1, Nicolai Franzmeier1, Endy Weidinger1
1From the Departments of Neurology (C.P., E.W., A.M.B., S.K., J.L., G.U.H.), Nuclear Medicine (S.W., C.F., S.H., J.S., S.S., J.G., A.F., G.B., S.L., N.L.A., P.B., M.B.), and Psychiatry and Psychotherapy (B.-S.R., R.P.) and the Institutes for Stroke and Dementia Research (N.F.) and Neuroradiology (B.-S.R.), University Hospital, LMU Munich, Germany; Munich Cluster for Systems Neurology (C.P., N.F., S.K., P.B., R.P., C.H., M.B., J.L.), SyNergy, Germany; German Center for Neurodegenerative Diseases (C.P., E.W., A.M.B., S.K., B.N., B.-S.R., R.P., C.H., M.B., J.L., G.U.H.), DZNE-Munich, Germany; Department of Nuclear Medicine (O.S., H.B.), Leipzig University Medical Centre; Department of Psychiatry and Psychotherapy (R.R.), University of Regensburg, Germany; Life Molecular Imaging GmbH (A.W.S.), Berlin, Germany; Sheffield Institute for Translational Neuroscience (SITraN) (B.-S.R., R.P.), University of Sheffield, United Kingdom; Ageing Epidemiology Research Unit (AGE) (R.P.), School of Public Health, Imperial College London, United Kingdom; and Chair of Metabolic Biochemistry (C.H.), Biomedical Center (BMC), Ludwig-Maximilians-Universität LMU, Munich, Germany.
Background And Objectives:
Corticobasal 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 β-amyloid (Aβ)-negative CBS.
Methods:
We included patients with clinically diagnosed Aβ-negative CBS with clinical follow-up data who underwent baseline structural MRI and plasma-NfL analysis for assessing neurodegeneration, [18F]PI-2620-PET for assessing tau pathology, [18F]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 × biomarker interaction).
Results:
Overall, 21 patients with Aβ-negative CBS with ∼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 [18F]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:
[18F]PI-2620 tau-PET, [18F]GE-180 TSPO-PET, and plasma-NfL show prognostic potential for clinical progression in patients with Aβ-negative CBS with probable 4-repeat tauopathy, which can be useful for clinical decision-making and stratifying patients in clinical trials.
