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Editorial commentary
In vivo tracking of TDP43 in ALS: cognition as a new biomarker for brain pathology
  1. Dorothée E Lulé1,
  2. Albert C Ludolph2
  1. 1 Department of Neurology, Neuropsychology, University of Ulm, Ulm, Germany
  2. 2 Department of Neurology, University of Ulm, Ulm, Germany
  1. Correspondence to Professor Albert C Ludolph, Neurology, University of Ulm, 89081 Ulm, Germany; albert.ludolph{at}rku.de

https://doi.org/10.1136/jnnp-2019-321940

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    The thought-provoking hypothesis has been empirically tested that cognitive deficits may be an indirect measure of cortical pTDP43 neuropathology

    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 …

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    Footnotes

    • Contributors Both authors fulfil the criteria for authorship.

    • Funding This is an EU Joint Programme–Neurodegenerative Disease Research (JPND) Project (’NEEDSinALS; www.NEEDSinALS.com; 01ED1405). The project is supported through the following organisations under the aegis of JPND - www.jpnd.eu: Germany, Bundesministerium für Bildung und Forschung (BMBF, FKZ). This work was additionally funded by the Deutsche Forschungsgemeinschaft (DFG, LU 336/13-2) and the Bundesministerium für Bildung und Forschung (MND-Net 01GM1103A; PaCeMed 01DS18031). DZNE.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Commissioned; internally peer reviewed.

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