Fig. 2

Depiction of the roles that have been described for glial cells in primary tauopathies. In the absence of amyloid pathology, early microgliosis may be initiated by neuronal tau seeds (1), though this remains to be thoroughly tested. Tau seeding has been found early in mouse models of tauopathy, and secreted, extracellular tau also possibly has seeding capability. Either direct or indirect consequences from tau seeds may be responsible for instigating the early microgliosis reported in tau mouse models. Activated microglia then secrete pro-inflammatory cytokines which further exacerbates microgliosis and co-activates astrocytes leading to toxic loss and gain of functions (2). Similar to the role proposed for AD, gliosis and inflammatory signaling can impact tau phosphorylation and possibly enhance misfolding and aggregation (3). In addition, astrocytic tau pathology characterizes several primary tauopathies such as PSP and CBD (4), though the functional consequences of the different aggregate phenotypes that are observed remain unknown. Spread of toxic tau species via microglial-associated exosomes is also a possible mechanism in primary tauopathies (5). Together, chronic neuroinflammation combined with tau pathology diminishes neuronal health and worsens neurodegeneration