{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:23:17Z","timestamp":1789698197894,"version":"4.0.1"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"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":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>The loss of von Economo neurons (VENs) and GABA receptor subunit theta (GABRQ) containing neurons is linked to early changes in social\u2013emotional cognition and is seen in frontotemporal dementia (FTD) due to <jats:italic>C9orf72<\/jats:italic> repeat expansion. We investigate the vulnerability of VENs and GABRQ\u2010expressing neurons in sporadic and genetic forms of FTD with different underlying molecular pathology and their association with the presence and severity of behavioural symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We quantified VENs and GABRQ\u2010immunopositive neurons in the anterior cingulate cortex (ACC) in FTD with underlying TDP43 (FTLD\u2010TDP) (<jats:italic>n<\/jats:italic>\u2009=\u200934), tau (FTLD\u2010tau) (<jats:italic>n<\/jats:italic>\u2009=\u200924) or FUS (FTLD\u2010FUS) (<jats:italic>n<\/jats:italic>\u2009=\u20098) pathology, neurologically healthy controls (<jats:italic>n<\/jats:italic>\u2009=\u200912) and Alzheimer's disease (AD) (<jats:italic>n<\/jats:italic>\u2009=\u20097). Second, we quantified VENs and the GABRQ\u2010expressing population in relation to presence of behavioural symptoms in the first years of disease onset.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The number of VENs and GABRQ\u2010expressing neurons and the ratio of VENs and GABRQ\u2010expressing neurons over total Layer 5 neuronal population decreased in FTLD\u2010TDP and FTLD\u2010FUS, but not in FTLD\u2010tau, compared to control and AD. The severity of early behavioural symptoms in all donors correlated with a lower VEN and GABRQ neuronal count.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We show that in FTD, a loss of VENs together with GABRQ\u2010expressing pyramidal neurons is associated with TDP43 and FUS pathology. No significant loss was found in donors with FTLD\u2010tau pathology; however, this could be due to the specific MAPT mutation studied and small sporadic FTLD\u2010tau sample size. Overall, we show the GABRQ\u2010expressing population correlates with behavioural changes and suggest they are key in modulating behaviour in FTD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12798","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T23:48:40Z","timestamp":1644796120000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The severity of behavioural symptoms in FTD is linked to the loss of GABRQ\u2010expressing VENs and pyramidal neurons"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5263-8706","authenticated-orcid":false,"given":"Priya","family":"Gami\u2010Patel","sequence":"first","affiliation":[{"name":"Department of Pathology, Amsterdam Neuroscience Amsterdam University Medical Centre  Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2420-6447","authenticated-orcid":false,"given":"Marta","family":"Scarioni","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam Neuroscience Amsterdam University Medical Centre  Amsterdam Netherlands"},{"name":"Department of Neurology, Alzheimer Centre, Amsterdam Neuroscience Amsterdam University Medical Centre  Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0527-2270","authenticated-orcid":false,"given":"Femke H.","family":"Bouwman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Alzheimer Centre, Amsterdam Neuroscience Amsterdam University Medical Centre  Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4922-3286","authenticated-orcid":false,"given":"Baayla D. 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