Neuroimmune dysfunction in frontotemporal dementia: Insights from progranulin and C9orf72 deficiency

Curr Opin Neurobiol. 2022 Oct:76:102599. doi: 10.1016/j.conb.2022.102599. Epub 2022 Jul 2.


Neuroimmune dysfunction is a cardinal feature of neurodegenerative diseases. But how immune dysregulation in the brain and peripheral organs contribute to neurodegeneration remains unclear. Here, we discuss the recent advances highlighting neuroimmune dysfunction as a key disease-driving factor in frontotemporal dementia (FTD). We provide an overview of the clinical observations supporting a high prevalence of autoimmune diseases in FTD patients with mutations in GRN or C9orf72. We then focus on a myriad of evidence from human genetic studies, mouse models, in vitro assays, and multi-omics platform, which indicate that haploinsufficiency in GRN and C9orf72 promotes neuroimmune dysfunction and contributes to neurodegeneration and premature death. These compelling data provide key insights to disease mechanisms, biomarker discovery, and therapeutic interventions for FTD (120 words).

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biomarkers
  • C9orf72 Protein* / genetics
  • Frontotemporal Dementia* / genetics
  • Humans
  • Mice
  • Mutation
  • Progranulins* / genetics


  • Biomarkers
  • C9orf72 Protein
  • C9orf72 protein, human
  • GRN protein, human
  • Progranulins