Multimodal Approach using MR and 18F-FDG-PET imaging in antemortem diagnosis of early stage TDP-43 Proteinopathy

Motivation: TDP-43, a 43kDa protein in the brain, plays a crucial role in neurodegenerative disorders and is a potential target for clinical trials. Confirmation currently requires an autopsy. Goal(s): To explore potential antemortem biomarkers for early-stage TDP-43 detection using conventional MRI and 18F-FDG-PET scans. Approach: Blinded visual evaluations of MRI and 18F-FDG-PET scans were performed utilizing specialized rating scales. Results: TDP-43(+) cases exhibited more medial temporal atrophy on MRI, though influenced by age. Visual inspection of MRI and 18F-FDG-PET changes could aid early TDP-43 prediction, although further research employing advanced neuroimaging and statistical techniques is essential to identify more robust early-stage TDP-43 neuroimaging biomarkers. Impact: Predicting TDP-43 status holds substantial diagnostic and clinical significance. TDP-43 could emerge as a promising therapy target in neurodegenerative disorders and a critical consideration in clinical trials. Early-stage TDP-43 prediction offers valuable insights into disease prognosis and progression.