Figure 3
Secreted Aβ x-40 and Aβ x-42 levels in the releasates of synaptoneurosomes following incubation with latrepirdine. Post-natal day 10-14 TgCRND8 cortical synaptoneurosomes were incubated 0 (baseline), 1, 3, 5, or 10 minutes in the presence of 1 μM (n = 5) or 10 μM (n = 6) latrepirdine. (a) 1 μM latrepirdine stimulates an increase in secretion of Aβx-42, but not Aβx-40, from isolated synaptoneurosomes following 3 minutes (SD = 0.06, t(4) = 2.81, p = 0.048) of incubation with the drug, and a decrease (~6%) is observed at 10 minutes (SD = 0.01, t(5) = 9.61, p = 0.0007), likely representing a depletion of available Aβx-42 (mean % baseline +/- S.E.M). (b) 10 μM latrepirdine stimulates an increase in secretion of Aβx-42, but not Aβx-40, following 1 (SD = 0.038, t(5) = 6.73, p = 0.001), 3 (SD = 0.028, t(5) = 7.35, p = 0.0007), and 5 (SD = 0.056, t(5) = 5.29, p = 0.0029) minutes of incubation with the drug (mean % baseline +/- S.E.M). (c) An immediate ~4.1% increase (SD = 0.13, t(5) = 3.205, p = 0.024) in Aβx-42/Aβx-40 ratio was observed following 1 minute of incubation with 10 μM latrepirdine (mean Aβx-42/Aβx-40). (Note: TgCRND8 mice generate ~50%/50% Aβx-42/Aβx-40 under normal conditions and the increase in Aβx-42/Aβx-40 ratio may be due to the large stimulation of Aβ secretion at this time point). *Value represents a significant mean difference between baseline and time-point by paired t-test, two-tailed α = 0.05, *p < 0.05, **p < 0.01.