Send to

Choose Destination
Brain. 2016 Dec;139(Pt 12):3202-3216. Epub 2016 Oct 22.

Timing and significance of pathological features in C9orf72 expansion-associated frontotemporal dementia.

Author information

1 Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94158, USA.
2 Department of Neurology, Eulji University Hospital, Eulji University School of Medicine, Daejeon 35233, South Korea.
3 Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL 32224, USA.
4 Department of Neurology and Department of Psychiatry, Semel Institute for Neuroscience and Human Behaviour, University of California, Los Angeles, CA 90095, USA.
5 Department of Pathology and Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA.
6 Epilepsy Center, Department of Neurology, University of California San Francisco, CA 94143, USA.
1 Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94158, USA
7 Department of Pathology, University of California, San Francisco, CA 94143, USA.


SEE SCABER AND TALBOT DOI101093/AWW264 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: A GGGGCC repeat expansion in C9orf72 leads to frontotemporal dementia and/or amyotrophic lateral sclerosis. Diverse pathological features have been identified, and their disease relevance remains much debated. Here, we describe two illuminating patients with frontotemporal dementia due to the C9orf72 repeat expansion. Case 1 was a 65-year-old female with behavioural variant frontotemporal dementia accompanied by focal degeneration in subgenual anterior cingulate cortex, amygdala, and medial pulvinar thalamus. At autopsy, widespread RNA foci and dipeptide repeat protein inclusions were observed, but TDP-43 pathology was nearly absent, even in degenerating brain regions. Case 2 was a 74-year-old female with atypical frontotemporal dementia-motor neuron disease who underwent temporal lobe resection for epilepsy 5 years prior to her first frontotemporal dementia symptoms. Archival surgical resection tissue contained RNA foci, dipeptide repeat protein inclusions, and loss of nuclear TDP-43 but no TDP-43 inclusions despite florid TDP-43 inclusions at autopsy 8 years after first symptoms. These findings suggest that C9orf72-specific phenomena may impact brain structure and function and emerge before first symptoms and TDP-43 aggregation.


TDP-43; frontotemporal dementia; protein aggregation

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center