The Function of Tau in Astrocytes: Advantage or Damage

The Tau protein is traditionally recognized for stabilizing axonal microtubules in neurons. However, emerging evidence indicates that astrocytes also show basal expression of the microtubule-associated protein Tau (MAPT) gene, with potential implications for central nervous system (CNS) homeostasis. Under physiological conditions, astrocytes support functions essential to CNS integrity, including metabolic support, neurotransmitter uptake, blood–brain barrier maintenance, and immune surveillance, all of which may be influenced by endogenous Tau expression. This review examines the current literature on the mechanisms that govern astrocytic Tau regulation, mainly in primary tauopathies with glial cytopathology. Available data indicate that Tau accumulation in these glial cells arises from endogenous synthesis, uptake from neighboring neurons, or a combination of these pathways, while failed extracellular clearance may favor this process by increasing Tau availability in the extracellular space. Once internalized, Tau can be processed, degraded through proteolytic and autophagic-lysosomal pathways, or re-released into the extracellular space, potentially facilitating its propagation; insufficient degradation, in contrast, promotes reactive astrogliosis and disrupts vital processes such as metabolic support and neurotransmitter handling. Taken together, this evidence suggests that distinguishing endogenous synthesis from neuronal uptake is essential to define glial-mediated pathology and recognize astrocytic Tau as a relevant contributor to neurodegenerative disease progression.