Impairment of Long-Term Potentiation in Alzheimer's Disease: A computational study based on tripartite synapse structure

In this work we propose a model to describe impairment of Long-Term Potentiation (LTP) due to Amyloid Beta (Aβ) accumulation during Alzheimer's Disease (AD) in hippocampus. The model embeds astrocyte-neuron interactions and Spike Timing-Dependent Plasticity (STDP) in CA3-CA1 synapses. In our proposed model, considering physiological facts, each astrocyte has a bidirectional signaling with four neurons, consisting of two pre-synaptic and two post-synaptic neurons. Sustained elevation in strength of each synapse leads to an increase in strength of other adjacent synapse, and finally to coupling between those synapses; this is known as LTP. We increased probability of pre-synaptic glutamate release to the level of reported experimental data on AD. As expected, increase of pre-synaptic glutamate release elevates astrocytic calcium. Due to excessive elevation of astrocytic calcium loss of calcium homeostatic, depression in synaptic strength, disruption of slow inward NMDA currents and finally impairment of LTP occur. Our results confirm the hypothesis that although calcium endocytosis is vital to induce LTP, fast and excessive increase of astrocytic calcium makes major problems and impairments for the LTP.