Fig. 4: Oral administration of DDL-357 increases sCLU levels and improves memory in AD mouse models. | npj Drug Discovery

Fig. 4: Oral administration of DDL-357 increases sCLU levels and improves memory in AD mouse models.

From: Discovery of a small molecule secreted clusterin enhancer that improves memory in Alzheimer’s disease mice

Fig. 4

A DDL-357 brain concentrations (total in blue and unbound in red), 1, 2, 4, 6 and 8 hours following oral administration at a dose of 30 mg/kg (n = 3 per time point). B sCLU levels in the hippocampus of ApoE4TR-5XFAD mice following subchronic, 2-week oral administration of DDL-357 at 15 mg/kg BID (n = 7 per group, DDL-357 - 4 females and 3 males; vehicle - 3 females and 4 males). For chronic 6-week testing of oral 15 mg/kg BID in the 3xTg-AD model: C phosphorylated tau (ptau)/total tau levels at S396 in the hippocampus (n = 13 per group, DDL-357 - 4 females and 9 males; vehicle - 5 females and 8 males), D scatter plot and Pearson correlation coefficients for the ptau/total tau ratio for S396 and S202/T205 vs. sCLU levels in the hippocampus, and E latency to escape hole (sec) in both training a probe trials in the Barnes Maze. All results graphed as mean ± SEM. The statistics for were performed using unpaired two-tailed t-test, where *p ≤ 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001). Pearson correlation coefficients.

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