Yue Yang1,2, Glenda M Halliday1,2,3, John R Hodges1,2,3, Rachel H Tan1,2,3. 1. Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney, Australia. 2. Neuroscience Research Australia, Sydney, Australia. 3. School of Medical Sciences, University of New South Wales, Sydney, Australia.
Abstract
BACKGROUND: The early and selective loss of von Economo neurons in the anterior cingulate cortex has been linked to behavioral deficits in frontotemporal dementia (FTD). Importantly, whether these neurons are also targeted in patients with the C9ORF72 repeat expansion has yet to be established. This is of particular interest given the recent evidence highlighting the thalamus rather than anterior cingulate cortex as a region of significant degeneration in patients with the C9ORF72 repeat expansion. OBJECTIVE: To assess the von Economo neuron density and thalamus volumes in behavioral variant FTD (bvFTD) cases with the C9ORF72 repeat expansion, sporadic bvFTD, sporadic ALS, and controls. METHODS: Volumetric and quantitative cell counting methods were employed to assess the von Economo neuron density and thalamus volumes in 37 pathologically-confirmed cases comprised of patients with bvFTD (n = 13) cases with the C9ORF72 repeat expansion (62% with psychosis), sporadic bvFTD (n = 8), sporadic amyotrophic lateral sclerosis (n = 7) and controls (n = 9). RESULTS: von Economo neuron density was significantly reduced in sporadic bvFTD cases only. Thalamus degeneration was identified only in bvFTD cases with the C9ORF72 repeat expansion, and to a similar extent in cases with and without psychosis. No significant difference in von Economo neuron density or thalamus degeneration was seen between bvFTD cases with or without the C9ORF72 repeat expansion. CONCLUSION: The present histological findings converge with neuroimaging results to corroborate the anterior cingulate cortex as a core region involved in sporadic bvFTD, and the thalamus as a major region targeted in patients with the C9ORF72 expansion.
BACKGROUND: The early and selective loss of von Economo neurons in the anterior cingulate cortex has been linked to behavioral deficits in frontotemporal dementia (FTD). Importantly, whether these neurons are also targeted in patients with the C9ORF72 repeat expansion has yet to be established. This is of particular interest given the recent evidence highlighting the thalamus rather than anterior cingulate cortex as a region of significant degeneration in patients with the C9ORF72 repeat expansion. OBJECTIVE: To assess the von Economo neuron density and thalamus volumes in behavioral variant FTD (bvFTD) cases with the C9ORF72 repeat expansion, sporadic bvFTD, sporadic ALS, and controls. METHODS: Volumetric and quantitative cell counting methods were employed to assess the von Economo neuron density and thalamus volumes in 37 pathologically-confirmed cases comprised of patients with bvFTD (n = 13) cases with the C9ORF72 repeat expansion (62% with psychosis), sporadic bvFTD (n = 8), sporadic amyotrophic lateral sclerosis (n = 7) and controls (n = 9). RESULTS:von Economo neuron density was significantly reduced in sporadic bvFTD cases only. Thalamus degeneration was identified only in bvFTD cases with the C9ORF72 repeat expansion, and to a similar extent in cases with and without psychosis. No significant difference in von Economo neuron density or thalamus degeneration was seen between bvFTD cases with or without the C9ORF72 repeat expansion. CONCLUSION: The present histological findings converge with neuroimaging results to corroborate the anterior cingulate cortex as a core region involved in sporadic bvFTD, and the thalamus as a major region targeted in patients with the C9ORF72 expansion.
Authors: Stacey Li Hi Shing; Mary Clare McKenna; We Fong Siah; Rangariroyashe H Chipika; Orla Hardiman; Peter Bede Journal: Brain Imaging Behav Date: 2021-01-05 Impact factor: 3.978
Authors: Lorenzo Pasquini; Alissa L Nana; Gianina Toller; Jesse A Brown; Jersey Deng; Adam Staffaroni; Eun-Joo Kim; Ji-Hye L Hwang; Libo Li; Youngsoon Park; Stephanie E Gaus; Isabel Allen; Virginia E Sturm; Salvatore Spina; Lea T Grinberg; Katherine P Rankin; Joel H Kramer; Howard J Rosen; Bruce L Miller; William W Seeley Journal: Cereb Cortex Date: 2020-09-03 Impact factor: 5.357
Authors: Martina Bocchetta; Juan E Iglesias; Mollie Neason; David M Cash; Jason D Warren; Jonathan D Rohrer Journal: Hum Brain Mapp Date: 2019-11-07 Impact factor: 5.038
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; Timo Grimmer Journal: Transl Psychiatry Date: 2019-01-31 Impact factor: 6.222
Authors: Li-Chun Lin; Alissa L Nana; Mackenzie Hepker; Ji-Hye Lee Hwang; Stephanie E Gaus; Salvatore Spina; Celica G Cosme; Li Gan; Lea T Grinberg; Daniel H Geschwind; Giovanni Coppola; Howard J Rosen; Bruce L Miller; William W Seeley Journal: Acta Neuropathol Commun Date: 2019-10-22 Impact factor: 7.801
Authors: P Gami-Patel; I van Dijken; J C van Swieten; Y A L Pijnenburg; A J M Rozemuller; J J M Hoozemans; A A Dijkstra Journal: Neuropathol Appl Neurobiol Date: 2019-06-10 Impact factor: 8.090
Authors: Martina Bocchetta; Elizabeth Gordon; M Jorge Cardoso; Marc Modat; Sebastien Ourselin; Jason D Warren; Jonathan D Rohrer Journal: Neuroimage Clin Date: 2018-02-23 Impact factor: 4.881