Beta amyloid-neuron interactions explored via computational modeling.

There has been considerable research into the mechanism by which beta amyloid (Abeta), one of the primary constituents in Alzheimer's disease, causes death in neurons. Many mechanisms have been proposed, and there is no consensus as to their validity. In order to aid in the comparison of various mechanisms, a computational model of a neuron was created. Research has shown that Abeta is capable of reducing the cell membrane's dielectric barrier by thinning the membrane. This reduction causes an increase in both membrane conductance and capacitance. This mechanism showed strong correlation to experimental data at low concentrations of Abeta. However, in the presence of Abeta in concentrations larger than 1.5microM, it was unable to produce results which agree with experimental data. If Abeta increases the conductance of a membrane, then it is likely through a different mechanism at higher concentrations. There has also been research into Abeta creating an ion channel inside the cell membrane, but no model of this channel yet exists. Using kinetic and equilibrium data from literature, a prototype model was created and implemented in the neuron. Although the results do not precisely match literature data, the prototype shows strong correlation with all of the trends expected when Abeta interacts with neurons. This shows that the Abeta channel has a distinct possibility of being a prime part of Abeta-neuron interactions and requires more research. This neuronal model has provided insight into two different mechanisms and can be used in the same manner for many others.