Disruption of IF network by tau accumulation in astrocytes recapitulate features of astrocytic pathology in human tauopathies. Double-label immunofluorescence staining for vimentin (Vim) and β-tubulin (Tub) before (A) and 8 hr after (B) T40-AV infection. Similar double labeling also was performed for GFAP and Tub before (D) and 8 hr after (E) T40-AV infection. Double labeling of tau (Tau) and Vim (C) or tau and GFAP (F) after T40-AV infection, as well as after GFP-AV infection (G, H). Note the collapse of the IF network and its accumulation on the vicinity of the nucleus 8 hr after T40-AV infection, even in the cells with preserved MT networks (B,E) with relatively low tau expression levels (C,F). A similar collapse of GFAP IF networks can be detected in a brain section from a patient with PSP immunostained with PHF1 and an anti-GFAP antibody (I). Note that the PHF1-positive astrocytes have lost their GFAP-positive long processes and exhibit a disrupted GFAP IF network in which there are abnormal tau accumulations (I, inset). Scale bars: A-I, 10 μm. Transmission EM shows the collapse of the IF network. Eight hours after T40-AV infection, low-power photomicrograph shows MT bundles in the cell periphery (J, arrow), and compacted IFs are seen in the vicinity of the nucleus (data not shown) but not in the peripheral area (J, white arrowhead). Higher magnification of MT bundles (K) and IFs (L) show exclusion of IFs in K and MTs in L, respectively. Scale bars: J-L, 100 nm.