Fig.5.

γ-secretase inhibition leads to earlier AβPP CTF accumulation at pre- than post-synaptic sites. A) In the CA3 region of hippocampus AβPP CTFs are mainly accumulating in post-synaptic compartments in PS1 cKO; AβPP Tg mice. Arrowheads denote post-synaptic densities. Scale bars 500 nm. B) Immunofluorescent labeling of AβPP/PS1 primary cortical neurons treated with the γ-secretase inhibitor DAPT. AβPP CTF-accumulation is seen by C-terminal specific AβPP antibody 369 in both axons and dendrites after 17 h. However, with only 2 h of DAPT treatment, AβPP CTF-accumulation is evident only in pre-synaptic compartments. Scale bars 50 μm. C) Quantification of the intensity of antibody 369 labeling in post-synaptic compared to pre-synaptic compartments with DAPT-treatment indicates a relatively greater increase in pre-synapses, which is also evident earlier (at 2 h). Thresholds were set by automatic thresholding by default on confocal images in the MAP2 or tau-1 channel. The mean intensity of the antibody 369 channel was subsequently measured in the pixels that were above threshold in the MAP2 or tau-1 channel respectively. Values are presented as percentage of respective untreated control.