Figure 7
From: Multi-compartmental modeling of SORLA’s influence on amyloidogenic processing in Alzheimer’s disease
Total amount of APP that is free, used, in monomer processing, and in dimer processing in each compartment. Simulations of the influence of intermediate levels of SORLA on APP processing into the amounts of APP concentrations in the TGN (A-E), at the cell surface (F-J), in the endosomes (K-O), and in all the three compartments (P-T). There are five intermediate levels of SORLA, namely, 0% (solid line), 3%, 12%, 30%, and 100% (dashed line) of SORLATot (where SORLATot = 2.43 x 105 fmol). When there is only solid line in a plot, it is because solid and dashed lines are superimposed. Note that the term “used” refers to the complex formation of (i) APP and SORLA in the TGN, (ii) APP and α-secretase at the cell surface, and (iii) APP and β-secretase in the endosomes. Wherein, the term “free” refers to the APP that is not bound in the respective compartments. The first two columns show the total amount of APP concentrations that is free and used. While in the third and fourth columns, the total amount of APP concentrations in monomer and in dimer processing are shown, respectively. Each line in the last column has double meaning: (i) the sum of the corresponding amount of APP concentrations shown in the first two columns, or (ii) the sum of the respective amount of APP concentrations shown in the third and fourth columns. The plots aligned along the first column show that SORLA significantly decreases the total amount of free APP concentrations in each compartment. The plots in the second column show that the total amount of APP concentrations in the TGN increases significantly (B), while unaffecting and minimally decreases those at the cell surface (G) and in the endosomes (L), respectively. As for the plots in the third column, they show that SORLA has no influence on the total amount of APP concentrations in monomer processing. Moreover to the plots in the fourth column, it is observed that as the level of SORLA concentration in dimer processing increases, the total amount of APP concentrations in the TGN also increases (D), while those at the cell surface (I) and in the endosomes decreases (N).