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Fig. 4 | Acta Neuropathologica Communications

Fig. 4

From: Aggregate-selective antibody attenuates seeded aggregation but not spontaneously evolving disease in SOD1 ALS model mice

Fig. 4

αSOD1143–153 detected in association to hSOD1 aggregates formed in the CNS. a, b Plots show antibody concentrations in plasma and CSF samples from hSOD1G85R Tg mice inoculated with aggregate seeds and treated with weekly i.p. mAb injections; 10 mg/kg αSOD1143–153 (pink triangles), 50 mg/kg αSOD1143–153 (red triangles), 50 mg/kg αSOD165–72 (green circles). αSOD1 mAb titres were determined by hSOD1 ELISA. a Blood samples were collected on the day of seed inoculation (d0); 1 day after the latest antibody injection, day 28 and day 56 after seed inoculation (d28, d56); 7 days after antibody injection. Values represent mean ± SD (n = 4–5 mice/group for each timepoint). b Scatter plot shows αSOD1 mAb concentration in CSF in relation to plasma level. Days post mAb injection varied depending on when the end-stage phenotype was reached. Both blood and CSF samples were collected at sacrifice. Mean CSF concentration was calculated to 0.3 μg/ml, 0.22% of plasma levels (10 mg/kg αSOD1143–153 (n = 4), 1.6 μg/ml, 0.25% of plasma levels in the 50 mg/kg αSOD1143–153 mice (n = 7) and 1.1 μg/ml, 0.26% of plasma levels in 50 mg/kg αSOD165–72 treated mice (n = 5). c Dot blot of cervical spinal cord homogenates from terminal stage non-, or mAb-treated mice probed with anti-mouse IgG (m-IgG) to monitor mAb binding in association to filter trapped aggregates (n = 3 mice/group). As control for aggregate load, the level of hSOD1 aggregates in each homogenate, was monitored using a polyclonal rbAb SOD157–72 (for quantification see Additional file 1: Figure S1). d Confocal images of the ventral horn of cervical spinal cord sections from αSOD1143–153 treated mice. Immunofluorescence labelling using anti-mouse IgG (m-IgG; green), SOD1 (red) and ChAT (blue) as a marker for MNs. Scalebars = 10 μm. In only a few occurrences, could IgG labelling be detected in association to hSOD1 aggregation in αSOD1143–153 treated animals. No IgG labelling was detected in association with hSOD1 aggregates in ChAT+ motor neurons

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