Connecting Epilepsy and Alzheimer’s Disease: Modeling of Normal and Pathological Rhythmicity and Synaptic Plasticity Related to Amyloid $$\beta $$ (A $$\beta $$ ) Effects

Abstract

This paper is motivated by the hidden links between neurodegeneration due to Alzheimer's disease and temporal lobe epileptic activity. β -amyloid peptides have multiple effects potentially at molecular, cellular, synaptic, network as well as system levels. To explore these links a computational framework was discussed, and two parts of the framework, i.e pathological rhythm generation and altered bidirec-tional synaptic plasticity have been constructed and analyzed. By using a skeleton network model of the hippocampal rhythm generation it was demonstrated how Aβ affects the ability of neurons in hippocampal networks to fire in unison at theta fre-quency resulting in reduced power of the theta rhythm. The dual qualitative effects of elevated Aβ at the synaptic level, i.e LTD facilitation and LTP impairment is studied by a modified calcium control hypothesis. The modification implemented the β -amyloid effects on the bidirectional synaptic plasticity and explained well the experimental findings of decreased LTP and increased LTD. The analysis of a kinetic model taking into account the phosphorylation and dephosphorylation pathways as-1