Abstract:

Ca²⁺ dysregulation is an early event observed in Alzheimer’s disease (AD) patients preceding the presence of its clinical symptoms. Dysregulation of neuronal Ca²⁺ will cause synaptic loss and neuronal death, eventually leading to memory impairments and cognitive decline. Treatments targeting Ca²⁺ signaling pathways are potential therapeutic strategies against AD. The complicated interactions make it challenging and expensive to study the underlying mechanisms as to how Ca²⁺ signaling contributes to the pathogenesis of AD. Computational modeling offers new opportunities to study the signaling pathway and test proposed mechanisms. In this mini-review, we present some computational approaches that have been used to study Ca²⁺ dysregulation of AD by simulating Ca²⁺ signaling at various levels. We also pointed out the future directions that computational modeling can be done in studying the Ca²⁺ dysregulation in AD.

Key words: Alzheimer’s disease, amyloid-beta, Ca2+ hypothesis, Ca2+ dysregulation, computational modeling, computational neuroscience