Figure 5. Diffusible extracellular Aβ concentration in vivo.

(A) Schematic illustration of model #2, which simulates diffusion of Aβ in the intact mouse brain and overlying agarose. The model included 2mm of brain tissue and 1 mm of agarose sealed with a coverslip. We calculated diffusion in the vertical axis (dashed line). (B) Initial concentration of Aβ as a function of location. The tissue-agarose boundary is at 2 mm. Initial concentration in the tissue is 1, with the result that Aβ concentration is normalized to the initial concentration in brain tissue. (C) Concentrations of monomer and 24mer (plot as a function of location) at 1 second, 1, 10 and 30 minutes, 1, 2, 3, 5, 10 and 30 hours. Half-life of Aβ was 1.28 hours. Black lines highlight concentrations at 1 hour and 10 hours. (D) Mean concentration of Aβ in the agarose, plot against time, for monomer and 24mer. After 30 hours monomer and 24mer are 96.5% and 82.2%, respectively, of the initial tissue concentration. Solid lines are double exponential fits to the results. Both curves are dominated by one exponential term with time constants of 8.9 hours for the monomer and 17 hours for the 24mer. (E) Tissue Aβ concentration in vivo, calculated from measurements of Aβ concentration in agarose. Each data point represents the mean and range from one mouse (n = 9 mice; 3–4 measurements per mouse). The line is a linear fit.