{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:02:16Z","timestamp":1790197336116,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T00:00:00Z","timestamp":1560124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["733050507"],"award-info":[{"award-number":["733050507"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The behavioural variant of frontotemporal dementia with a <jats:italic>C9orf72<\/jats:italic> expansion (C9\u2010bv<jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content>) is characterised by early changes in social\u2010emotional cognition that are linked to the loss of von Economo neurons (<jats:styled-content style=\"fixed-case\">VEN<\/jats:styled-content>s). Together with a subset of neighbouring pyramidal neurons, <jats:styled-content style=\"fixed-case\">VEN<\/jats:styled-content>s express the <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content> receptor subunit theta (<jats:styled-content style=\"fixed-case\">GABRQ<\/jats:styled-content>). It is not known if the selective vulnerability of <jats:styled-content style=\"fixed-case\">VEN<\/jats:styled-content>s in C9\u2010bv<jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content> also includes this <jats:styled-content style=\"fixed-case\">GABRQ<\/jats:styled-content>\u2010expressing population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We quantified <jats:styled-content style=\"fixed-case\">VEN<\/jats:styled-content>s and <jats:styled-content style=\"fixed-case\">GABRQ<\/jats:styled-content> immunopositive neurons in the anterior cingulate cortex (<jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>) in C9\u2010bv<jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content> (<jats:italic>n<\/jats:italic>\u00a0=\u00a016), controls (<jats:italic>n<\/jats:italic>\u00a0=\u00a012) and Alzheimer's disease (<jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>) (<jats:italic>n<\/jats:italic>\u00a0=\u00a07). Second, we assessed <jats:styled-content style=\"fixed-case\">VEN<\/jats:styled-content>s and <jats:styled-content style=\"fixed-case\">GABRQ<\/jats:styled-content>\u2010expressing populations in relation to the clinicopathological profiles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found the number of <jats:styled-content style=\"fixed-case\">VEN<\/jats:styled-content>s and <jats:styled-content style=\"fixed-case\">GABRQ<\/jats:styled-content>\u2010expressing neurons and their ratio over the total layer 5 neuronal population was lower in C9\u2010bv<jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content> compared to control and <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>. C9\u2010bv<jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content> donors with underlying <jats:styled-content style=\"fixed-case\">TDP<\/jats:styled-content>43 type A pathology in the <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content> showed the highest loss of <jats:styled-content style=\"fixed-case\">GABRQ<\/jats:styled-content>\u2010expressing neurons. C9\u2010bv<jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content> donors that did not present with motor neuron disease (<jats:styled-content style=\"fixed-case\">MND<\/jats:styled-content>) symptoms in the first half of their disease course showed a prominent loss of <jats:styled-content style=\"fixed-case\">GABRQ<\/jats:styled-content>\u2010expressing neurons compared to controls. C9\u2010bv<jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content> donors with no symptoms of psychosis showed a higher loss compared to controls. Across all donors, the number of <jats:styled-content style=\"fixed-case\">VEN<\/jats:styled-content>s correlated strongly with the number of <jats:styled-content style=\"fixed-case\">GABRQ<\/jats:styled-content>\u2010expressing neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We show that <jats:styled-content style=\"fixed-case\">VEN<\/jats:styled-content>s, together with <jats:styled-content style=\"fixed-case\">GABRQ<\/jats:styled-content>\u2010expressing neurons, are selectively vulnerable in C9\u2010bv<jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content> but are both spared in <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>. This suggests they are related and that this <jats:styled-content style=\"fixed-case\">GABRQ<\/jats:styled-content>\u2010expressing population of <jats:styled-content style=\"fixed-case\">VEN<\/jats:styled-content>s and pyramidal neurons, is a key modulator of social\u2010emotional functioning.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12558","type":"journal-article","created":{"date-parts":[[2019,5,8]],"date-time":"2019-05-08T04:23:33Z","timestamp":1557289413000},"page":"671-680","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Von Economo neurons are part of a larger neuronal population that are selectively vulnerable in C9orf72 frontotemporal dementia"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5263-8706","authenticated-orcid":false,"given":"P.","family":"Gami\u2010Patel","sequence":"first","affiliation":[{"name":"Department of Pathology Amsterdam Neuroscience Amsterdam University Medical Centre Location VUMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"van Dijken","sequence":"additional","affiliation":[{"name":"Department of Pathology Amsterdam Neuroscience Amsterdam University Medical Centre Location VUMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. C.","family":"van Swieten","sequence":"additional","affiliation":[{"name":"Department of Neurology Alzheimer Centre Erasmus MC Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. A. L.","family":"Pijnenburg","sequence":"additional","affiliation":[{"name":"Department of Neurology Alzheimer Centre Amsterdam Neuroscience Amsterdam University Medical Centre Location VUMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Netherlands Brain Bank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. J. M.","family":"Rozemuller","sequence":"additional","affiliation":[{"name":"Department of Pathology Amsterdam Neuroscience Amsterdam University Medical Centre Location VUMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. J. M.","family":"Hoozemans","sequence":"additional","affiliation":[{"name":"Department of Pathology Amsterdam Neuroscience Amsterdam University Medical Centre Location VUMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. A.","family":"Dijkstra","sequence":"additional","affiliation":[{"name":"Department of Pathology Amsterdam Neuroscience Amsterdam University Medical Centre Location VUMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/09540261.2013.776523"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.09.011"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006344"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1476-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1679-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0845-8"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws324"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21055"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhr004"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170002"},{"key":"e_1_2_9_12_1","first-page":"64","article-title":"Greater loss of von Economo neurons than loss of layer II and III neurons in behavioral variant frontotemporal dementia","volume":"3","author":"Santillo AF","year":"2014","journal-title":"Am J Neurodegener Dis"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12021"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903550106"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02970950"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.20829"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22055"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2011.06011.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw358"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.9.5268"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr361"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1253-7"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0673-2"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020936"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.08.067"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2018.00064"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.02.048"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e3283168e2d"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.003"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2011.05990.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-008-0434-7"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1716-8"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-017-0480-2"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1942-8"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-10-03588.2000"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00033-7"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.02.043"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.17.9891"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12558","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nan.12558","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12558","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T15:38:44Z","timestamp":1694187524000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.12558"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,10]]},"references-count":37,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["10.1111\/nan.12558"],"URL":"https:\/\/doi.org\/10.1111\/nan.12558","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,10]]},"assertion":[{"value":"2019-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}