Acta Neuropathologica

, Volume 138, Issue 6, pp 1093–1097 | Cite as

C9orf72-specific phenomena associated with frontotemporal dementia and gastrointestinal symptoms in the absence of TDP-43 aggregation

  • Paul J. Sampognaro
  • Sarat C. Vatsavayai
  • Celica G. Cosme
  • Ji-Hye L. Hwang
  • Amber Nolan
  • Eric J. Huang
  • William W. SeeleyEmail author
  • Mary G. De May

The most common genetic cause of frontotemporal dementia is the expanded hexanucleotide (GGGGCC) repeat insertion in a non-coding promoter region of the chromosome 9 open reading frame 72 (C9orf72) gene [4, 13]. Nearly all patients who carry the C9orf72 expansion show well-developed TAR DNA-binding protein 43 (TDP-43) inclusion pathology at autopsy, and TDP-43 has been considered a key driver of neurodegeneration based on human clinicopathological correlation approaches [7]. Scattered case reports describing pre-symptomatic C9orf72 expansion carriers suggest, however, that C9orf72-specific phenomena such as dipeptide repeat (DPR) proteins and RNA foci can be observed in the absence of or even preceding TDP-43 inclusions [11, 15]. One previous report of a patient with behavioral variant FTD (bvFTD) suggested that focal degeneration could occur in brain regions lacking TDP-43 aggregation, but to date no patient with symptomatic C9orf72-associated “probable” FTD has lacked TDP-43...



The authors wish to thank the patient and her family for their invaluable contributions to neurodegeneration research. The authors also wish to thank Dr. Leonard Petrucelli and his group at the Mayo Clinic Florida for contributing dipeptide repeat protein antibodies. This work was supported by NIH grants AG023501 and AG019724, the Tau Consortium, and the Bluefield Project to Cure FTD.

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Conflict of interest

The authors have no conflicts of interest relevant to this article to disclose.

Supplementary material

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Supplementary material 1 (DOCX 13643 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Department of PathologyUniversity of California, San FranciscoSan FranciscoUSA

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