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J. Neurosci. (2009) 29(34): 10741-9), and in which the native mouse Tau gene was deleted, were used to assess pharmacodynamic endpoints and tissue drug concentrations. Brain tissue (right, frontal cortical region) was collected on dry ice or RNAlater for drug concentration analysis and Tau qPCR respectively at multiple time points following dosing, e.g., 1 week through 16 weeks post-dosing. A second 5 minute post addition plate read (300 one second points) on the FLIPR was conducted to allow for additional data capture. Calculations were performed by measuring the average FLIPR signal over the 300 second read for control (non-treated) wells. Oligomers were added with a 384 well head in the FLIPR in 20 .mu.l of assay buffer at 75 .mu.M for a final concentration of 25 .mu.M. Data presented in FIG. 1 show that, addition of the AMPA receptor antagonist, 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX; 3 .mu.M), reduced calcium oscillations by 20% representing the total AMPA response in the assay (FIG. 1AMPA labeled bar shown).

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