You are here

Article Text

Article menu
Neurodegeneration
Short report
In vivo PET imaging of neuroinflammation in familial frontotemporal dementia
  1. Maura Malpetti1,
  2. Timothy Rittman1,
  3. Peter Simon Jones1,
  4. Thomas Edmund Cope1,
  5. Luca Passamonti1,2,
  6. William Richard Bevan-Jones3,
  7. Karalyn Patterson1,
  8. Tim D Fryer1,4,
  9. Young T Hong1,4,
  10. Franklin I Aigbirhio1,4,
  11. John Tiernan O'Brien3,
  12. James Benedict Rowe1,5
  1. 1 Department of Clinical Neurosciences, and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, Cambridgeshire, UK
  2. 2 Istituto di Bioimmagini e Fisiologia Molecolare Consiglio Nazionale delle Ricerche, Milan, Italy
  3. 3 Department of Psychiatry, University of Cambridge, Cambridge, Cambridgeshire, UK
  4. 4 Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, Cambridgeshire, UK
  5. 5 Medical Research Council Cognition and Brain Sciences Unit, Cambridge, Cambridgeshire, UK
  1. Correspondence to Dr James Benedict Rowe, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 1TN, Cambridgeshire, UK; James.Rowe{at}mrc-cbu.cam.ac.uk

Abstract

Introduction We report in vivo patterns of neuroinflammation and abnormal protein aggregation in seven cases of familial frontotemporal dementia (FTD) with mutations in MAPT, GRN and C9orf72 genes.

Methods Using positron emission tomography (PET), we explored the association of the distribution of activated microglia, as measured by the radioligand [11C]PK11195, and the regional distribution of tau or TDP-43 pathology, indexed using the radioligand [18F]AV-1451. The familial FTD PET data were compared with healthy controls.

Results Patients with familial FTD across all mutation groups showed increased [11C]PK11195 binding predominantly in frontotemporal regions, with additional regions showing abnormalities in individuals. Patients with MAPT mutations had a consistent distribution of [18F]AV-1451 binding across the brain, with heterogeneous distributions among carriers of GRN and C9orf72 mutations.

Discussion This case series suggests that neuroinflammation is part of the pathophysiology of familial FTD, warranting further consideration of immunomodulatory therapies for disease modification and prevention.

  • frontotemporal dementia
  • PET
  • genetics
https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/jnnp-2020-323698

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Supplementary materials

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Footnotes

    • JTO and JBR are joint senior authors.

    • Twitter @timrittman

    • Correction notice This article has been corrected since it appeared Online First. Author name has been corrected from Thomas Edward Cope, to Thomas Edmund Cope.

    • Contributors Conceptualisation and design: MM, FIA, JBR, JTO; data analysis: MM, PSJ, TDF, YTH; methodology: MM, TR, PSJ, TEC, LP, TDF, YTH, JBR; interpretation: MM, TR, JBR, JTO; data collection: TR, TEC, LP, WRB-J, KP, TDF, YTH, FIA; first draft: MM, TR; supervision: JBR and JTO. All authors revised and approved the final version of the manuscript.

    • Funding This study was co-funded by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre; the Wellcome Trust (103838); the Medical Research Council (MR/P01271X/1); a Cambridge Trust & Sidney Sussex College Scholarship; and the Cambridge Centre for Parkinson-Plus.

    • Competing interests JBR reports consultancy unrelated to the work with Biogen, UCB, Asceneuron and Althira; and receipt of research grants from Janssen, AZ-Medimmune, Lilly unrelated to this work. JTO has provided consultancy to TauRx, Axon, Roche, GE Healthcare and Lilly; and has research awards from Alliance Medical and Merck. TR has received honoraria from the National Institute for Health and Clinical Excellence, Oxford Biomedica and Learna Ltd.

    • Patient consent for publication Not required.

    • Ethics approval The study was approved by the National Research Ethics Service East of England Cambridge Central Committee. Written informed consent was obtained from all participants.

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

    Linked Articles