NeuroMab™ Anti-TDP43 BBB Shuttle Antibody(NRZP-1022-ZP2633)

Fig.1 Density of pTDP-43 immunoreactive objects measured for the vehicle (n = 30, grey bars) and ACI-7069-633B12-AM (IgG2a variant) treated mice (n = 25, dotted grey bars) are shown for two brain regions.

Immunofluorescent staining of human TDP-43 and TDP-43 oligomers in the brain slices of wild type and 6- and 12-month-old TDP-43 Tg+/+ transgenic mice. Cells with anti-TDP oligomer staining, TDP-43 staining, and DAPI staining are shown (scale bar, 100 μιη). Blocked area was presented at higher magnification in the last column (scale bar, 25 μιη).

Fig.2 TDP-43 aggregation induced by TEV cleavage in the presence of ACI-7069-633B12-AM (IgG2a variant) or isotype control is measured by turbidity at 600 nm after 30 h.

Endpoints after 30h were normalized to isotype control (grey bar) and % aggregated TDP-43 was calculated for ACI-7069- 633B12-AM (dotted grey bar). Mean values ± SD are shown for three independent experiments and statistical differences between isotype control and ACI-7069-633B12-AM (IgG2a variant) were analyzed by Welch's t-tests (***p < 0.001).

Fig.3 Ibal positive immunoreactive area measured for vehicle (n = 16, grey bars) and ACI- 7069-633B12-AM (IgG2a variant) treated mice (n = 16, dotted grey bars) is shown for brain cortex. Error bars represents standard error of mean (SEM).

Endpoints after 30h were normalized to isotype control (grey bar) and % aggregated TDP-43 was calculated for ACI-7069- 633B12-AM (dotted grey bar). Mean values ± SD are shown for three independent experiments and statistical differences between isotype control and ACI-7069-633B12-AM (IgG2a variant) were analyzed by Welch's t-tests (***p < 0.001).

Fig.4 Quantification of TDP-43 levels in CSF of various FTLD-TDP patients versus healthy controls with AlphaLISA assay with ACI-7069-633B12-AM (IgG2a variant) and ACI-7071-809F12- Abl (IgG2a variant).

Endpoints after 30h were normalized to isotype control (grey bar) and % aggregated TDP-43 was calculated for ACI-7069- 633B12-AM (dotted grey bar). Mean values ± SD are shown for three independent experiments and statistical differences between isotype control and ACI-7069-633B12-AM (IgG2a variant) were analyzed by Welch's t-tests (***p < 0.001).

Fig.5 Immunodepletion of TDP-43 and pTDP-43 by the antibodies ACI-7069-633B12-AM (IgG2a variant) (1), ACI-7069-642D12-AM (IgG2a variant).

Endpoints after 30h were normalized to isotype control (grey bar) and % aggregated TDP-43 was calculated for ACI-7069- 633B12-AM (dotted grey bar). Mean values ± SD are shown for three independent experiments and statistical differences between isotype control and ACI-7069-633B12-AM (IgG2a variant) were analyzed by Welch's t-tests (***p < 0.001).