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Fig. 6 | Alzheimer's Research & Therapy

Fig. 6

From: Blood–brain barrier penetrating neprilysin degrades monomeric amyloid-beta in a mouse model of Alzheimer’s disease

Fig. 6

Concentrations in the brain, blood and peripheral organs after administration of [125I]sNEP-scFc-scFv8D3, [125I]muNEP-scFc-scFv8D3 and [125I]scFc-scFv8D3 at therapeutic doses of 30 nmol/kg body weight to 7–8 month-old tg-ArcSwe mice. A. Graphical figure of the experimental setup. B Significantly lower brain retention of [125I]sNEP-scFc-scFv8D3 and [125I]muNEP-scFc-scFv8D3 compared to [125I]scFc-scFv8D3 at 72 h post-injection. C Significantly lower plasma concentrations of [125I]sNEP-scFc-scFv8D3 and [125I]muNEP-scFc-scFv8D3 compared to [125I]scFc-scFv8D3, 72 h post-injection. D Brain-to-plasma concentration ratio of the three recombinant proteins at 72 h post-injection which illustrates transport to and from the brain. E Blood pharmacokinetics of the three injected proteins. Shorter half-lives were detected for [125I]sNEP-scFc-scFv8D3 and [125I]muNEP-scFc-scFv8D3 compared to [125I]scFc-scFv8D3. Values given in brackets. F Total drug exposure in blood, expressed as the area under the curve (AUC) of the three injected proteins. Fivefold lower blood exposure for [125I]sNEP-scFc-scFv8D3 and [125I]muNEP-scFc-scFv8D3 compared to [.125I]scFc-scFv8D3. G Biodistribution of the three injected proteins in peripheral organs at 72 h post-injection. Results are presented as mean ± SD (mean ± SEM for AUC results in E). One-way ANOVA with Bonferroni’s multiple comparison test was applied (n = 4/sNEP-scFc-scFv8D3 and muNEP-scFc-scFv8D3; n = 3/scFc-scFv8D3) (p > 0.05 = ns; p ≤ 0.05 = *; p ≤ 0.01 = **; p ≤ 0.001 = ***)

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