FDG-PET underscores the key role of the thalamus in frontotemporal lobar degeneration caused by C9ORF72 mutations.

Abstract

C9ORF72 mutations are the most common cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). MRI studies have investigated structural changes in C9ORF72-associated FTLD (C9FTLD) and provided first insights about a prominent involvement of the thalamus and the cerebellum. Our multicenter, 18F-fluorodeoxyglucose positron-emission tomography study of 22 mutation carriers with FTLD, 22 matched non-carriers with FTLD, and 23 cognitively healthy controls provided valuable insights into functional changes in C9FTLD: compared to non-carriers, mutation carriers showed a significant reduction of glucose metabolism in both thalami, underscoring the key role of the thalamus in C9FTLD. Thalamic metabolism did not correlate with disease severity, duration of disease, or the presence of psychotic symptoms. Against our expectations we could not demonstrate a cerebellar hypometabolism in carriers or non-carriers. Future imaging and neuropathological studies in large patient cohorts are required to further elucidate the central role of the thalamus in C9FTLD.

• Authors: Janine Diehl-Schmid, Abigail Licata, Oliver Goldhardt, Hans Förstl, Igor Yakushew, Markus Otto, Sarah Anderl-Straub, Ambros Beer, Albert Christian Ludolph, Georg Bernhard Landwehrmeyer, Johannes Levin, Adrian Danek, Klaus Fliessbach, Annika Spottke, Klaus Fassbender, Epameinondas Lyros, Johannes Prudlo, Bernd Joachim Krause, Alexander Volk, Dieter Edbauer, Matthias Leopold Schroeter, Alexander Drzezga, Johannes Kornhuber, Martin Lauer, FTLDc Study Group, Timo Grimmer
• Journal: Translational psychiatry (Transl Psychiatry) Vol. 9 Issue 1 Pg. 54 (01 31 2019) ISSN: 2158-3188 [Electronic] United States
• PMID: 30705258 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• C9orf72 Protein
• C9orf72 protein, human
• Fluorodeoxyglucose F18

Topics

• Aged
• C9orf72 Protein (genetics)
• Cerebellum (diagnostic imaging, metabolism)
• Female
• Fluorodeoxyglucose F18
• Frontotemporal Lobar Degeneration (diagnostic imaging, genetics, metabolism)
• Humans
• Male
• Middle Aged
• Mutation
• Positron-Emission Tomography
• Sensitivity and Specificity
• Thalamus (diagnostic imaging, metabolism)