Fig. 7.

Model of β-arrestin2-promoted tauopathy in FTLD. In healthy brains, monomeric β-arrestin2 regulates GPCR trafficking, and there is no excess of oligomeric β-arrestin2 and thus misfolded tau is efficiently ubiquitylated and targeted for autophagy clearance. However, in FTLD-tau brains, β-arrestin2 oligomers are increased, inhibiting p62-mediated autophagy, leading to failure of misfolded/aggregated tau to be efficiently cleared. In AD, the increased β-arrestin2 also results in an increase in Aβ amyloid (not illlustrated).