Entorhinal cortex astrocytic atrophy in human frontotemporal dementia

The pathophysiology of Fronto Temporal Dementia (FTD) remains poorly understood, specifically the role of astroglia. Our aim was to explore the hypothesis of astrocytic alterations as a component for FTD pathophysiology. We performed an in-depth tri-dimensional (3-D) anatomical and morphometric study of glial fibrillary acidic protein (GFAP)-positive and glutamine synthetase (GS)-positive astrocytes in the human entorhinal cortex (EC) of FTD patients. The studies at this level in the different types of human dementia are scarce. We observed a prominent astrocyte atrophy of GFAP-positive astrocytes and co-expressing GFAP/GS astrocytes, characterised by a decrease in area and volume, whilst minor changes in GS-positive astrocytes in FTD compared to non-dementia controls (ND) samples. This study evidences the importance of astrocyte atrophy and dysfunction in human EC. We hypothesise that FTD is not only a neuropathological disease, but also a gliopathological disease having a major relevance in the understanding the astrocyte role in FTD pathological processes and development.