Figure 6-9. Model of plaque formation and neuronal death in Alzheimer’s disease. From Edelstein-Keshet and Spiros, 2002 : Top row: Formation of a plaque and death of neurons in the absence of glial cells, when fibrous amyloid is the only injurious influence. The simulation was run with no astrocytes or microglia, and the health of neurons was determined solely by the local fibrous amyloid. Shown above is a time sequence (left to right) of three stages in plaque development, at early, intermediate, and advanced stages. Density of fibrous deposit is represented by small dots and neuronal health by shading from white (healthy) to black (dead). Note radial symmetry due to simple diffusion. Bottom row: Effect of microglial removal of amyloid on plaque morphology. Note that microglia (small star-like shapes) are seen approaching the plaque (via chemotaxis to soluble amyloid, not shown). At a later stage, they have congregated at the plaque center, where they adhere to fibers. As a result of the removal of soluble and fibrous amyloid, the microglia lead to irregular plaque morphology. Size scale: In this figure, the distance between the small single dots (representing low-fiber deposits) is 10 mm. Similar results were obtained for a 10-fold scaling in the time scale of neuronal health dynamics.

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