The severity of behavioural symptoms in FTD is linked to the loss of GABRQ-expressing VENs and pyramidal neurons.
Neuropathol Appl Neurobiol
; 48(4): e12798, 2022 06.
Article
en En
| MEDLINE
| ID: mdl-35152451
ABSTRACT
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.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Demencia Frontotemporal
/
Enfermedad de Alzheimer
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
Neuropathol Appl Neurobiol
Año:
2022
Tipo del documento:
Article