The growth rate of senile plaques is determined by the competition between the rate of deposition of free Aβ aggregates into plaques and the autocatalytic production of free Aβ aggregates

The formation of amyloid beta (A{beta}) deposits (senile plaques) is one of the hallmarks of Alzheimers disease (AD). This study investigates what processes are primarily responsible for their formation. A model is developed to simulate the diffusion of amyloid beta (A{beta}) monomers, the production of free A{beta} aggregates through nucleation and autocatalytic processes, and the deposition of these aggregates into senile plaques. The model suggests that efficient degradation of A{beta} monomers alone may suffice to prevent the growth of senile plaques, even without degrading A{beta} aggregates and existing plaques. This is because the degradation of A{beta} monomers interrupts the supply of reactants needed for plaque formation. The impact of A{beta} monomer diffusivity is demonstrated to be small, enabling the application of the lumped capacitance approximation and the derivation of approximate analytical solutions for limiting cases with both small and large rates of A{beta} aggregate deposition into plaques. It is found that the rate of plaque growth is governed by two competing processes. One is the deposition rate of free A{beta} aggregates into senile plaques. If this rate is small, the plaque grows slowly. However, if the rate of deposition of A{beta} aggregates into senile plaques is very large, the free A{beta} aggregates are removed from the intracellular fluid by deposition into the plaques, leaving insufficient free A{beta} aggregates to catalyze the production of new aggregates. This suggests that under certain conditions, A{beta} plaques may offer neuroprotection and impede their own growth. Additionally, it indicates that there exists an optimal rate of deposition of free A{beta} aggregates into the plaques, at which the plaques attain their maximum size.