Fig. 5: Therapeutic efficacy of a plaque-evading lithium salt.
From: Lithium deficiency and the onset of Alzheimer’s disease
a, Organic Li salt solutions exhibit lower conductivity than inorganic Li salts. All solutions contained 430 µEq l−1 Li. b,c, Li binds to human Aβ1–42 fibrils (b) and oligomers (c). Binding curves are shown for all tested concentrations (b, left) and the 0–30 µEq l−1 range (b, right). LiC shows higher affinity than LiO (EC50 values and 95% confidence intervals are in Supplementary Table 13). d, Immunolabelling of Aβ and pSer202-tau in the hippocampus (left) and quantification of plaque burden (middle) and pSer202-tau+ cell density (right) in 3xTg mice treated with LiO or LiC (4.3 µEq l−1) from 9 to 18 months of age (vehicle n = 3, LiC n = 11, LiO n = 13). e, Aβ immunolabelling (left) and quantification (right) in J20 mice treated with LiO (4.3 µEq l−1) from 17 to 22 months of age (water n = 9, LiO n = 11). f, GO analysis of DEGs from RNA-seq analysis of the hippocampus of 3xTg mice treated with LiO (4.3 µEq l−1) or vehicle from 6 to 12 months of age (n = 9 per group). g, Memory retrieval in the Morris water maze for 3xTg mice treated from 5 to 12 months of age; WT mice (12 months) served as controls. WT n = 16, 3xTg n = 25, LiO 4.3 n = 17, LiO 430 n = 16 (left), n = 15 (right), LiC n = 10, NaO n = 9. In d,e, data were normalized to the mean for the water vehicle. In a–c, mean ± s.d. values are shown from n = 3 independent solution replicates (a) or n = 3 biological replicates (b,c). In d,e,g, box plots show individual values, median (line), box limits (25th and 75th percentiles) and whiskers (minimum and maximum). In d,e, P values were calculated by one-way ANOVA with Tukey’s post-hoc test. In g, WT and 3xTg (water) groups were compared using a preplanned unpaired two-tailed t-test; all other P values were derived from one-way ANOVA with Dunnett’s post-hoc comparisons to the 3xTg (water) control. Scale bars, 50 μm.
