Objective: A head-to-head comparison of neuroimaging (tau-PET, microglia-PET, structural MRI) and plasma biomarker Neurofilament light chain (NfL) as prognostic tools for longitudinal clinical trajectories in amyloid-negative Corticobasal Syndrome (CBS).

Background: CBS with underlying 4-repeat tauopathy is a progressive neurodegenerative disease with declining cognitive and motor functions. Biomarkers for assessing pathological brain changes in CBS declining cognitive and motor functions. Biomarkers for assessing pathological brain changes in CBS including tau-PET, microglia-PET, structural MRI and NfL have recently been evaluated for differential diagnosis and disease staging, yet the potential of these biomarkers for predicting disease trajectories remains unclear.

Method: We included 21 clinically diagnosed amyloid-negative CBS patients with ~2-year clinical follow-up data who underwent baseline structural MRI, [¹⁸F]PI-2620 tau-PET, [¹⁸F]GE-180-PET and plasma-NfL analysis. To quantify tau and microglia load we assessed summary scores of whole-brain, cortical and subcortical PET signal. For structural MRI, we quantified subcortical and cortical grey matter volume. Plasma-NfL values were assessed using a Simoa-based immunoassay. Symptom progression was determined using a battery of cognitive and motor tests. 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).

Results: Overall, there was rapid decline on the assessed clinical scores. CBS patients with higher global tau-PET signal showed faster clinical progression, driven by cortical rather than subcortical tau-PET. In contrast, patients with higher global [¹⁸F]GE-180-PET readouts showed slower clinical progression. No association was found between grey matter volume and clinical progression. Higher plasma-NfL was prognostic of faster clinical deterioration.

Conclusion: [¹⁸F]PI-2620 tau-PET, [¹⁸F]GE-180 microglia-PET and plasma-NfL show prognostic potential for clinical progression in CBS patients with probable 4-repeat tauopathy, which can be useful for clinical decision making as well as stratifying patients in clinical trials.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neurofilament-light-chain-tau-pet-and-microglia-pet-predict-clinical-progression-in-amyloid-negative-corticobasal-syndrome/