Timing and significance of pathological features in C9orf72 expansion-associated frontotemporal dementia
Year: 2016
Type: article
Abstract: 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.
Source: Brain
DOI: 10.1093/brain/aww250
Authors: Sarat C. Vatsavayai, Soo Jin Yoon, Raquel C. Gardner, Tania F. Gendron, Jose Norberto S. Vargas, Andrew Trujillo, Mochtar Pribadi, Joanna J. Phillips, Stephanie E. Gaus, John D. Hixson, Paul A. Garcia, Gil D. Rabinovici, Giovanni Coppola, Daniel H. Geschwind, Leonard Petrucelli, Bruce L. Miller, William W. Seeley
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: TDP-43, RNA Metabolism, and ALS/FTD Pathology, Misregulation of the TDP-43 RNA target, Sortilin, in neurodegeneration, c9RAN proteins as a biomarker for C9ORF72-associated ALS and FTD, Traumatic Brain Injury and The Aging Brain: Predictors of Clinical Trajectories, Stress Granules and the Biology of TDP-43, Pathobiology of Neurodegeneration in C9ORF72 repeat expansion, RNA foci in C9FTD/ALS, Silencing C9or72 with rAAV Mediated RNAi, G9000036492, G9000052518, Frontotemporal Dementia: Genes, Images, and Emotions, UCSF Older Americans Independence Center, New Approaches to Dementia Heterogeneity, Mayo Alzheimer's Disease Research Center
OpenAlex ID: W2534857558