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Von Economo neurons are part of a larger neuronal population that are selectively vulnerable in C9orf72 frontotemporal dementia

Publication year 2019
Published in Neuropathology and Applied Neurobiology
Authors A.J.M. Rozemuller, Priya Gami-Patel, Irene van Dijken, John C van Swieten, Yolande A L Pijnenburg, Jeroen J M Hoozemans, Anke A Dijkstra,

AIMS: The behavioural variant of frontotemporal dementia with a C9orf72 expansion (C9-bvFTD) is characterised by early changes in social-emotional cognition that are linked to the loss of von Economo neurons (VENs). Together with a subset of neighbouring pyramidal neurons, VENs express the GABA receptor subunit theta (GABRQ). It is not known if the selective vulnerability of VENs in C9-bvFTD also includes this GABRQ-expressing population.

METHODS: We quantified VENs and GABRQ immunopositive neurons in the anterior cingulate cortex (ACC) in C9-bvFTD (n=16), controls (n=12) and Alzheimer’s disease (AD) (n=7). Second, we assessed VENs and GABRQ-expressing populations in relation to the clinicopathological profiles.

RESULTS: We found the number of VENs and GABRQ-expressing neurons and their ratio over the total layer 5 neuronal population was lower in C9-bvFTD compared to control and AD. C9-bvFTD donors with underlying TDP43 type A pathology in the ACC showed the highest loss of GABRQ-expressing neurons. C9-bvFTD donors that did not present with motor neuron disease (MND) symptoms in the first half of their disease course showed a prominent loss of GABRQ-expressing neurons compared to controls. C9-bvFTD donors with no symptoms of psychosis showed a higher loss compared to controls. Across all donors, the number of VENs correlated strongly with the number of GABRQ-expressing neurons.

CONCLUSION: We show that VENs, together with GABRQ-expressing neurons, are selectively vulnerable in C9-bvFTD but are both spared in AD. This suggests they are related and that this GABRQ-expressing population of VENs and pyramidal neurons, is a key modulator of social-emotional functioning.

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