Astrocytes and neuropsychiatric symptoms in neurodegenerative diseases: Exploring the missing links

Neurodegenerative diseases (NDs) are characterized by primary symptoms, such as cognitive or motor deficits. In addition, the presence of neuropsychiatric symptoms (NPS) in patients with ND is being increasingly acknowledged as an important disease feature. Yet, their neurobiological basis remains unclear and mostly centered on neurons while overlooking astrocytes, which are crucial regulators of neuronal function underlying complex behaviors. In this opinion article, we briefly review evidence for NPS in ND and discuss their experimental assessment in preclinical models. We then present recent studies showing that astrocyte-specific dysfunctions can lead to NPS. Because many astrocyte alterations are also observed in ND, we suggest that they might underlie ND-associated NPS. We argue that there is a need for dedicated preclinical studies assessing astrocyte-based therapeutic strategies targeting NPS in the context of ND.