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Von Economo neurons are part of a larger neuronal population that are selectively vulnerable in C9orf72 frontotemporal dementia
Author(s) -
GamiPatel P.,
Dijken I.,
Swieten J. C.,
Pijnenburg Y. A. L.,
Rozemuller A. J. M.,
Hoozemans J. J. M.,
Dijkstra A. A.
Publication year - 2019
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12558
Subject(s) - frontotemporal dementia , c9orf72 , population , neuroscience , ven , psychology , dementia , medicine , disease , humanities , environmental health , philosophy
Aims The behavioural variant of frontotemporal dementia with a C9orf72 expansion (C9‐bv FTD ) is characterised by early changes in social‐emotional cognition that are linked to the loss of von Economo neurons ( VEN s). Together with a subset of neighbouring pyramidal neurons, VEN s express the GABA receptor subunit theta ( GABRQ ). It is not known if the selective vulnerability of VEN s in C9‐bv FTD also includes this GABRQ ‐expressing population. Methods We quantified VEN s and GABRQ immunopositive neurons in the anterior cingulate cortex ( ACC ) in C9‐bv FTD ( n = 16), controls ( n = 12) and Alzheimer's disease ( AD ) ( n = 7). Second, we assessed VEN s and GABRQ ‐expressing populations in relation to the clinicopathological profiles. Results We found the number of VEN s and GABRQ ‐expressing neurons and their ratio over the total layer 5 neuronal population was lower in C9‐bv FTD compared to control and AD . C9‐bv FTD donors with underlying TDP 43 type A pathology in the ACC showed the highest loss of GABRQ ‐expressing neurons. C9‐bv FTD 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‐bv FTD donors with no symptoms of psychosis showed a higher loss compared to controls. Across all donors, the number of VEN s correlated strongly with the number of GABRQ ‐expressing neurons. Conclusion We show that VEN s, together with GABRQ ‐expressing neurons, are selectively vulnerable in C9‐bv FTD but are both spared in AD . This suggests they are related and that this GABRQ ‐expressing population of VEN s and pyramidal neurons, is a key modulator of social‐emotional functioning.