Figure 4. Pharmacokinetics and target engagement of antibodies at pre-amyloid stages.

(a) Schematic overview of antibody titer measurements. Six-month-old male transgenic (tg) APP23 mice or 6-month-old male wildtype (wt) mice received intraperitoneally 0.5 mg of either Beta1, m266, or cmAducanumab (cmAdu) on 5 consecutive days (n=5/group/antibody). Mice were analyzed 1, 7, or 21 days post-immunization (dpi). (b) Plasma logarithmic changes (Ln) in antibody concentration over time (days) in APP23 and wild-type mice. For Beta1 in the tg group, there were 1 and 4 mice below detection at 7 and 21 dpi, respectively. (c) Calculated elimination rate (k_el) and half-life (t_1/2) of antibody elimination in plasma suggest binding of Beta1 and m266 to blood Aβ, thus accelerating removal from blood, whereas no such acceleration is seen for cmAdu. Antibody titer assays were optimized for best detection of different monoclonal antibodies (see Methods). To exclude the possibility that different assay conditions affected the results, Beta1 titers were also measured with the cmAdu setup; however, similar accelerated antibody elimination was observed in tg vs wt mice (Beta1: t_1/2= 4.7 and 1.8, respectively). All data are represented as group means ± SEMs. No detectable titers of Aβ antibodies were found in untreated six-month-old or Ctrl-antibody-treated APP23 mice (see extended Data Fig. 4).