Study of dynamical properties of senile plaques: Amyloid beta deposition as a function of time

The goal is to study the dynamical properties of Amyloid beta in the process of deposition and formation, as a function of time, of senile plaques. Senile plaques are macroscopic aggregates of amyloid beta protein of 40-42 amino acids in length. The biological model of AD used is the transgenic mice that has been genetically modified so that their brains produce abnormally big amounts of amyloid.

The transgenice mouse offers the ideal setting for the time development study of the formation of plaques because the plaques can be studied at precise stages of development. This offers a great advantage over human (post mortem) tissue samples that can only give a view of a particular age of the individual.

In the study of the brains of transgenic mice, the amyloid deposits form clusters, also found in human AD brains. By sacrificing the transgenic mice at different stages of development, a study of the clustering formation as a function of time has been done.

In addition to the experimental observation of the clustering, we have modeled the dynamic evolution of the clusters using a cellular automata model. Our aggregation--disaggregation model is based on birth--death type of growth models. We have constructed it such that it accounts for both a dynamic equilibrium and a specific porous structure of the observed senile plaques. At each simulation step the rules for aggregation and disaggregation are applied to each particle in the lattice, thus mimicking the time evolution of particles. A particle in our terminology means an aggregate composed of many Abeta peptides, but at the same time it is much smaller compared to a fully evolved senile plaque. One can think of a particle as a fibril of amyloid beta peptide as experimentally observed.