One of the most prominent clinical symptoms of FTD is behavioral changes. A variant characterized by alterations in complex thinking, personality, and behavior is the behavioral variant of FTD (bvFTD). In patients with bvFTD, there is a selective loss of the GABA receptor subunit theta (GABRQ) expressing cortical neurons in the anterior cingulate cortex. These GABRQ-expressing neurons include the von Economo neurons (VENs).

Researchers Gami-Patel, Dijkstra, and colleagues of Amsterdam Neuroscience investigated whether there is a loss of GABRQ expressing neurons in the anterior cingulate cortex in the different pathological and genetic subtypes of FTD. Next to this, they studied the link between the number of GABRQ-expressing neurons and the early manifestations of behavioral symptoms. They quantified VENs and GABRQ-immunopostive neurons in the anterior cingulate cortex in FTD with different underlying pathologies, neurologically healthy controls, and Alzheimer’s disease. Secondly, they quantified the relation to the presence of behavioral symptoms in the first years of disease onset.

Their study showed a loss of VENs and GABRQ-expressing neurons in FTD donors with underlying TDP34 and fused in sarcoma (FUS) pathology but not in the subclass with tau pathology. The expressing neurons are also significantly lower in the FTD groups, but not in the Alzheimer’s disease group. This may indicate that these neurons are specifically linked with FTD. When looking at the clinical presentation, Gami-Patel and Dijkstra showed that FTD donors with more behavioral symptoms correlate with GABRQ-expressing neurons. This supports the hypothesis that these neurons are a key modulator of behavior in FTD.

Read the publication in Neuropathology and Applied Neurobiology: The severity of behavioural symptoms in FTD is linked to the loss of GABRQ-expressing VENs and pyramidal neurons