Simulation of Ca2+oscillations in astrocytes mediated by amyloid beta in Alzheimer’s disease

Disruptions of astrocyte Ca 2+ signaling is important in Alzheimer’s disease (AD) with the unclear mechanism of amyloid beta peptide (Aβ). We have modified our previous computational model of spontaneous Ca 2+ oscillations in astrocytes to investigate the effects of Aβ on intracellular Ca 2+ dynamics. The simulation results have shown consistence with the previous experiments. Aβ can increase the resting concentration of intracellular Ca 2+ and change the regime of Ca 2+ oscillations by activating L-type voltage-gated calcium channels and the metabolic glutamate receptors, or by increasing ryanodine receptors sensitivity and Ca 2+ leakage, respectively. This work have provided a toolkit to study the influence of Aβ on intracellular Ca 2+ dynamics in AD. It is helpful for understanding the toxic role of Aβ during the progression of AD. Statement of Significance Alzheimer’s disease (AD) is the most common neurodegenerative disease with the unclear mechanism of amyloid beta peptide (Aβ). This work have implemented a computational model to address the Ca 2+ dynamics of astrocyte mediated by Aβ with the four different pathways: voltage-gated calcium channels, metabotropic glutamate receptors 5, ryanodine receptor channels and membrane leak. The Ca 2+ oscillations and bifurcation diagram indicate that astrocytes exhibit ionic excitability mediated by Aβ and become the potential targets of Aβ neurotoxicity. We expect this shared computational model would advance the understanding of AD.