Prognostic value of Neurofilament light chain, [18F]‐PI2620 PET and [18F]GE‐180‐PET in amyloid‐negative Corticobasal Syndrome.

Autor: Palleis, Carla, Franzmeier, Nicolai, Weidinger, Endy, Bernhardt, Alexander, Katzdobler, Sabrina, Finze, Anika, Nuscher, Brigitte, Rauchmann, Boris‐Stephan, Perneczky, Robert, Haass, Christian, Brendel, Matthias, Levin, Johannes, Höglinger, Günter
Zdroj: Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2023 Supplement 16, Vol. 19, p1-2, 2p
Abstrakt: Background: Corticobasal syndrome (CBS) with underlying 4‐repeat tauopathy is a progressive neurodegenerative disorder characterized by declining cognitive and motor functions. Biomarkers for assessing pathological brain changes in CBS including tau‐ and microglia‐PET or neurofilament light chain (NfL) have recently been evaluated for differential diagnosis and disease staging, yet the prognostic accuracy of these biomarkers for predicting disease trajectories remains unclear. To address this, we performed a head‐to‐head comparison of neuroimaging (tau‐PET, microglia‐PET) and plasma biomarker NfL as prognostic tools for future clinical trajectories in 21 CBS patients with longitudinal clinical data. Method: We included 21 clinically diagnosed CBS patients with ∼2‐year clinical follow‐up data who underwent baseline [18F]PI‐2620‐PET for assessing tau pathology, [18F]GE‐180‐PET for microglia activation and plasma‐NfL for neurodegeneration. All patients were negative on amyloid biomarkers. To quantify tau and microglia load we assessed summary scores of whole‐brain, cortical and subcortical tracer signal. NfL was assessed using immunoassays on the Simoa platform. 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 progression of symptoms over time (i.e. time x biomarker interaction). Result: Overall, there was on average a rapid decline over time on the assessed clinical scores. For tau‐PET, CBS patients with higher global tau load showed faster clinical progression. This time x tau‐PET interaction was driven by cortical rather than subcortical tau‐PET load. Patients with higher [18F]GE‐180‐PET whole‐brain load showed slower clinical progression. Concerning plasma biomarker NfL, higher plasma‐NfL was prognostic of faster clinical deterioration. In a subsequent sensitivity analysis, we found that tau‐PET, microglia‐PET as well as plasma‐NfL showed significant (i.e. p<0.05) interaction effects with time on clinical trajectories when tested in the same model, suggesting that these biomarkers explain unique variability in future disease trajectories. 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. [ABSTRACT FROM AUTHOR]
Databáze: Supplemental Index