The Influence of Amyloid-Beta on Calcium Dynamics in Alzheimer’s Disease: A Spatio-Temporal Study

Data‐driven stochastic model for quantifying the interplay between amyloid‐beta and calcium levels in Alzheimer's disease

“…In other words, the shift to the pathological steady state cannot be reversed by a short‐duration of $$$ {Ca}^{+2} $$$ rise, which is a characteristic of the model that makes sense given that, without this feature, every action potential would lead to an increase in $$$ A\beta $$$ as discussed in Ref. [8, 9]. Yet, because of positive feedback and the rapid development of $$$ A\beta $$$, any noise‐induced rise in $$$ A\beta $$$ will also generate an increase in $$$ {Ca}^{+2} $$$, reinforcing the initial increase in $$$ A\beta $$$ [40].…”

“…The availability of tools for AD modeling has been relatively restricted thus far, likely because of the immense complexity of the molecular systems involved in its development [40]. Many mathematical models have previously been constructed to explore particular and well‐defined features of the disease [9, 16, 17, 18]. To the best of our knowledge, none of the computational models have been proposed yet to explore the synaptic interplay between $$$ A\beta $$$ and $$$ {Ca}^{+2} $$$ using clinical data.…”

“…The availability of tools for AD modeling has been relatively restricted thus far, likely because of the immense complexity of the molecular systems involved in its development [40]. Many mathematical models have previously been constructed to explore particular and well-defined features of the disease [9,16,17,18].…”

“…Many medication therapies are shown to slow the progression of AD, but there is no permanent cure [3–7]. The clinical and pathological hallmarks of AD include progressive neuronal loss, synaptic degradation, and the formation of amyloid plaques and neurofibrillary tangles in particular regions of the brain [8, 9]. According to some findings, AD may be a systemic disease since it affects not only neurons but also peripheral cells such as fibroblasts, lymphocytes, and platelets in AD patients [10–12].…”

“…According to the amyloid cascade theory, $$$ A\beta $$$ oligomers or amyloid fibrils are formed by the aggregation of $$$ A\beta $$$ oligomers or amyloid fibrils, which are key components of $$$ A\beta $$$ peptide and impair the function of neuronal cells [8]. Many mathematical models have been presented to explain the development of $$$ A\beta $$$ monomer synthesis or aggregation (see [9, 16–18] and the references therein). Another hypothesis that has attracted a lot of attention, proposes that disturbance of calcium $$$ \left({Ca}^{+2}\right) $$$ homeostasis is crucial to AD pathogenesis [19–21].…”