Aβ42 O (1µM) Surface  1 Total  1 A B ** 25 A β42 M FITC- A β42 M A β42 O FITC- A β42 O A β42 M A β42 Di A β42 Tri A β42 Tet - + C Supplemental Fig. S1

# # # Supplemental Fig. S2

Vinculin Actin Vinculin Actin Aβ42 O (µM) B h 4h Cyto FC C ** * Tubulin Vinc Talin Tubulin Vinc Talin - + A FC Cyto Aβ42 O Supplemental Fig. S3 D APP/PS1WT Scale bar 30μm * * E * Focal Vinculin / Cytosolic Vinculin FC Vinculin (% Cont)

Cyto FC Aβ42 O Cof siR Cofilin P-Cof Vinculin Cofilin P-Cof Vinculin AB ** Supplemental Fig. S4 FC Vinc (% Cont)

NC (n=4)AD (n=5) Gender 2M & 2F2M & 3F Age Range Average Age (+SD) PMI Range (h) Average PMI (+SD) Supplemental Fig. S5

VehicleAβ42 O (1uM) Nox inhibitorHUTS-4MAB1965Vehicle H2DCF Supplemental Fig. S6 A

Aβ42 O +  1 IgG Aβ42 O Control Annexin V DAPI PI / DAPI B C * * H Control A  42 O A  42 O + MAB1965 PI D Supplemental Fig. S6 Continued

P-Cof Actin Aβ42 O Veh MAB1965Trolox IP: SSH1 B Lysate Cof SSH1 Beads Supplemental Fig. S7 A Aβ42 O C beads Cof SSH1 IP: SSH1 Cof Lysate IP D ** Beads IP:

Supplemental Fig. S8 Cofilin Actin WT Cofilin +/- HIPPO CTX WT GFAP DAPI PSD95 DAPI Synapsin I Cofilin+/- A DG CA1 CA3 Scale bar 300μm CA3 SL B