Fig. 7: CP2 treatment after the onset of AD-like neuropathology halts progressive degeneration of LC neurons in APP/PS1 mice.

APP/PS1 and NTG mice were treated with CP2 or vehicle starting at 10 months of age. The animal brains were harvested at 12 (2 months treatment) or 20 months of age (10 months treatment) and evaluated for the integrity of the NAergic neurotransmitter system. a CP2 stops the progressive loss of TH⁺ axons in the cortex of 20-month-old mice APP/PS1 mice. Representative images of TH⁺ axonal projections in S1BF. Scale bar, 20 µm. b The density (µm/mm³) of TH⁺ axons in S1BF was determined using stereological length estimation using spherical probe and images presented in a. Compared to NTG mice, APP/PS1 mice exhibit a significant progressive loss of TH⁺ axons at 12 and 20 months of age. CP2 treatment prevented loss of TH⁺ axons in APP/PS1 mice occurs between 12 and 20 months of age. c Representative image of TH⁺ LC neurons in 20-month-old mice. Scale bar, 100 µm. d CP2 stops the progressive loss of TH⁺ neurons in APP/PS1 mice in LC. e Higher magnification images from c were used to evaluate the relative sizes of neurons. Scale bar, 50 µm. f CP2 stops the progressive loss of TH⁺ neuronal volume in APP/PS1 mice at 20 months of age. n = 6 female mice per group. Data are presented as mean ± S.E.M. A two-way ANOVA with Fisher’s LSD post-hoc test was used to analyze the differences between APP/PS1 mice, and between untreated groups of NTG and APP/PS1 mice. A Student t-test was used to analyze the differences between untreated and CP2-treated NTG mice. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.