Figure 1.

The impact of astrocytes on tau propagation in AD. Neurons contain tau on their microtubules (Yamada, 2017). Tau can become hyperphosphorylated and dissociate from the microtubules due to a myriad of factors (Mandelkow and Mandelkow, 2012; Fichou et al., 2019). Stimulated or dying neurons can release tau into the extracellular space (Pooler et al., 2013; Wu et al., 2016; Pernègre et al., 2019) 14-16, where astrocytes are known to internalize tau (de Calignon et al., 2012; Asai et al., 2015; Martini-Stoica et al., 2018; Perea et al., 2018, 2019). Astrocytic internalization rates may be affected by a number of factors, including cholesterol levels; APOE status; and tau concentration, aggregation state, and isoform. Following internalization, astrocytes may (1) degrade the internalized tau, (2) release the tau back out of the cell, potentially propagating the pathological tau to healthy neurons, and (3) accumulate tau, potentially triggering inflammatory cytokine release, which can harm neuronal health.