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second biosimulation test used a combination of 25 mM brain derived neurotrophic factor (BDNF) and 10 m M NGF as a continuous exposure for 60 min duration; this approach evaluated stimulation of p75 NTR, TrkA, and TrkB. Based on the human microarray results demonstrating downregulation of TrkA (50%) and TrkB (60%), the corresponding parameters in the TTR biosimulation were decreased by the same amount. Results: Baseline results were validated from published literature on neuronal calcium levels mediated via the phospholipase C-g and inositol-3-phosphate pathway at both bolus doses of NGF alone. With the corresponding parameters decreased in the TTR biosimulation, Figure 1: A) The reaction flux for c-RAF1 phosphorylation of MEK1 was delayed to peak value by 1.5 min from exposure, but the peak value was increased to 5 times the baseline value; B) Moreover, a slight shift to the right of the flux over time was observed with the B-RAF phosphorylation of MEK1. Conclusions: These biosimulation results indicate that the transient response to neurotrophins is accentuated, whereas the sustained MEK activating pathway is blunted in AD, and may be potential mechanisms for the failure of pro-survival pathways in AD.

phosphorylation at sites Ser199/202, Thr231/Ser235 and Ser396/404 but not at sites Thr212/Ser214. Since it was reported that As could affect synaptic NMDA responses, we analyzed the effect of As on tau phosphorylation. In this regard, we found that As increases tau phoshorylation at sites Thr231/ Ser235 and Ser396/404 but not at sites Ser199/202 and Thr212/Ser214 after five days incubation in hippocampal slice cultures.Conclusions:Our results suggest a common pathway between As and NMDA receptor activation. Furthermore our data showed that tau phosphorylation caused by NMDA receptor activation is occluded by prior incubation with As.