Skip to main content
. 2023 Dec 14;24(24):17478. doi: 10.3390/ijms242417478

Figure 7.

Figure 7

Hypothetical explanation of the prolonged recovery observed in the AD mouse model treated with ICV everolimus [30]. On the left, a cognitively impaired 3xTg-AD mouse. On the right, a cognitively recovered 3xTg-AD mouse. On the upper part of the figure, the in vitro production of βA-specific Tregs is described: (A) in vitro conditioning of DCs with βA and a rapalog [8,9,10,11,12,13], (B) injection of conditioned DCs into the bloodstream, (C) conditioned DCs migrate to regional lymph nodes; (D) infusion into the bloodstream of specific Tregs into 3xTg-AD mouse; (E) the infusion of βA-specific Tregs leads to improved βA tolerance and cognitive recovery [46] (green arrow), but not to βA load reduction (red arrow). On the bottom part of the figure, the in vivo approach and the hypothetical explanation of its rapid and prolonged efficacy are described [30,47]. (AB) The rapalog-loaded osmotic pump is implanted into the lateral ventricle, likely leading to conditioning of CNS-patrolling DCs; (C) conditioned DCs migrate to regional lymph nodes; (D) the treatment might lead to in vivo βA-specific Treg production that could lead to both βA tolerance [46] (green arrow) and to reduction of the βA load, promoting autophagy (F). The combined effect could explain the results observed.