The severity of behavioural symptoms in FTD is linked to the loss of GABRQ-expressing VENs and pyramidal neurons

Netherlands Brain Bank, Netherlands Brain Bank

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3 Citations (Scopus)


AIMS: The loss of von Economo neurons (VENs) and GABA receptor subunit theta (GABRQ) containing neurons is linked to early changes in social-emotional cognition and is seen in frontotemporal dementia (FTD) due to C9orf72 repeat expansion. We investigate the vulnerability of VENs and GABRQ-expressing neurons in sporadic and genetic forms of FTD with different underlying molecular pathology and their association with the presence and severity of behavioural symptoms.

METHODS: We quantified VENs and GABRQ-immunopositive neurons in the anterior cingulate cortex (ACC) in FTD with underlying TDP43 (FTLD-TDP) (n=34), tau (FTLD-tau) (n=24), or FUS (FTLD-FUS) (n=8) pathology, neurologically healthy controls (n=12) and Alzheimer's disease (AD) (n=7). Second, we quantified VENs and the GABRQ-expressing population in relation to presence of behavioural symptoms in the first years of disease onset.

RESULTS: The number of VENs and GABRQ-expressing neurons and the ratio of VENs and GABRQ-expressing neurons over total Layer 5 neuronal population decreased in FTLD-TDP and FTLD-FUS, but not in FTLD-tau, compared to control and AD. The severity of early behavioural symptoms in all donors correlated with a lower VEN and GABRQ neuronal count.

CONCLUSION: We show that in FTD, a loss of VENs together with GABRQ-expressing pyramidal neurons is associated with TDP43 and FUS pathology. No significant loss was found in donors with FTLD-tau pathology; however, this could be due to the specific MAPT mutation studied and small sporadic FTLD-tau sample size. Overall, we show the GABRQ-expressing population correlates with behavioural changes and suggest they are key in modulating behaviour in FTD.

Original languageEnglish
Article numbere12798
Pages (from-to)1-9
Number of pages9
JournalNeuropathology and applied neurobiology
Issue number4
Early online date13 Feb 2022
Publication statusPublished - 1 Jun 2022


  • frontotemporal dementia (FTD)
  • social–emotional behaviour
  • von Economo neuron (VEN)

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