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Brain 18fluorodeoxyglucose-positron emission tomography changes in amyotrophic lateral sclerosis with TARDBP mutations
  1. Antonio Canosa1,2,3,
  2. Andrea Calvo1,2,4,
  3. Cristina Moglia1,2,
  4. Rosario Vasta1,
  5. Francesca Palumbo1,
  6. Giuseppe Fuda1,
  7. Francesca Di Pede1,
  8. Sara Cabras1,
  9. Vincenzo Arena5,
  10. Andrea Novara1,
  11. Paolina Salamone1,
  12. Enrico Matteoni1,
  13. Luca Sbaiz6,
  14. Salvatore Gallone2,
  15. Maurizio Grassano1,
  16. Umberto Manera1,2,
  17. Adriano Chiò1,2,3,4,
  18. Marco Pagani3,7
  1. 1 ALS Centre, ‘Rita Levi Montalcini’ Department of Neuroscience, University of Turin, Turin, Italy
  2. 2 SC Neurologia 1U, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
  3. 3 Institute of Cognitive Sciences and Technologies, C.N.R, Rome, Italy
  4. 4 Neuroscience Institute of Turin (NIT), Turin, Italy
  5. 5 Positron Emission Tomography Centre AFFIDEA-IRMET S.p.A, Turin, Italy
  6. 6 Laboratory of Genetics, Department of Clinical Pathology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
  7. 7 Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden
  1. Correspondence to Dr Antonio Canosa, 'Rita Levi Montalcini' Department of Neuroscience, ALS Centre, University of Turin, Turin 10126, Italy; antonio.canosa{at}

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Amyotrophic lateral sclerosis (ALS) is a motor neuron degenerative disorder, causing death within 2–5 years from onset. In 2008, mutations of TARDBP gene, encoding for TDP-43, were identified as cause of familial ALS and sporadic ALS.1 The cytoplasmic inclusions of hyperphosphorylated TDP-43 within neurons and glia in the motor cortex is the neuropathological hallmark in ~95% of ALS cases, with the exception of those with SOD1 and FUS mutations.2 In a population-based study, the presence of TARDBP mutations was associated with an increased frequency of a predominantly upper motor neuron (UMN) phenotype.3 Currently, neuroimaging studies evaluating in vivo the extent of the neurodegenerative process in patients with TARDBP mutations (TARDBP-ALS) are limited, highlighting frontotemporal changes in cases with cognitive-behavioural impairment.4

We aimed to assess the brain metabolic changes associated with TARDBP-ALS, performing brain 18fluorodeoxyglucose positron emission tomography (18F-FDG-PET).

Materials and methods


We considered eligible patients carrying the TARDBP p.A382T mutation, diagnosed with genetically determined ALS according to El Escorial revised diagnostic criteria at the ALS Centre of Turin (‘Rita Levi Montalcini’ Department of Neuroscience, University of Turin, Italy), between 2009 and 2019, who underwent brain 18F-FDG-PET at diagnosis. Out of 17 eligible subjects, 2 were excluded because they also carried the hexanucleotide expansion of C9ORF72. Furthermore, we excluded one subject with frontotemporal dementia (FTD), possibly representing an outlier since FTD associated with ALS has a strong impact on brain metabolism. We included 14 patients without mutations in other major ALS-related genes (SOD1 and FUS).

We randomly collected 46 patients diagnosed with definite, probable, and probable laboratory-supported ALS according to El Escorial revised diagnostic criteria from the cohort of 665 subjects who underwent brain 18F-FDG-PET at diagnosis in the same period at the ALS Centre of Turin. This group (control ALS) included …

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  • AC and MP contributed equally.

  • Contributors Study concept and design: ACan, MP and ACh. Acquisition of data: ACan, ACal, CM, RV, FP, GF, FDP, SC, VA, AN, PS, EM, LS, SG, MG and UM. Analysis and interpretation of data: ACan, MP and ACh. Drafting of the manuscript: ACan, MP and ACh. Critical revision of the manuscript for important intellectual content: ACan, ACal, CM, RV, FP, GF, FDP, SC, VA, AN, PS, EM, LS, SG, MG and UM. Obtained funding: MP, ACh. Administrative, technical and material support: ACan, ACal, CM, RV, FP, GF, FDP, SC, VA, AN, PS, EM, LS, SG, MG and UM. Study supervision: ACan, MP and ACh. ACan had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors have approved the submitted version of the article. The information reported in the manuscript has never been reported elsewhere.

  • Funding This work was supported by the Progetti di Rilevante Interesse Nazionale (PRIN) 2017 (grant 2017SNW5MB) and the Joint Programme-Neurodegenerative Disease Research (Strength, ALS-Care and Brain-Mend projects), granted by the Italian Ministry of Education, University and Research; a grant from the Thierry Latran Foundation (INSPIRED project); the Italian Ministry of Health (Ricerca Sanitaria Finalizzata, grant RF-2016-02362405); the European Commission’s Health Seventh Framework Programme (FP7/2007-2013, grant agreement 259867). This study was performed under the Department of Excellence grant of the Italian Ministry of Education, University and Research to the ‘Rita Levi Montalcini’ Department of Neuroscience, University of Turin.

  • Competing interests ACal has received a research grant from Cytokinetics. ACh serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Biogen, Cytokinetics, Denali Therapeutics, Amylyx and AveXis.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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