In vivo tracking of TDP43 in ALS: cognition as a new biomarker for brain pathology

There is a lack of in vivo readout measures to track changes in brain pathology during the course of amyotrophic lateral sclerosis (ALS) which might support the measurement of therapeutic effects in clinical trials. For this, biomarkers need to be specific, reproducible and sensitive to changes in the course of the disease. Established clinical markers of motor deficits are the ALS functional rating scale (ALSFRS-R) and survival. Markers such as neurofilament light chain levels and MRI have been shown to be powerful candidates but have not been introduced into routine yet. Phosphorylated TDP43 (pTDP43) accumulations are reliable postmortem biomarkers of disease pathology in the majority of ALS autopsies and are related to cell death.1 Molecular pTDP43 load has limited use as a biomarker for clinical trials as it can be retrieved post mortem only and not in biological fluids. A completely new …