Computational Model to Analyze Calcium Imbalances in Cells Affected by Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a fatal neurodegenerative disorder that causes progressive memory impairment. It steadily erodes a person's ability to learn, think, and communicate. In 2019, over 50 million people were living with AD globally, and it is projected that this will increase to 82 million by 2030 and to 152 million by 2050.One proposed mechanism for causing neuronal cell death in AD is beta-amyloid. Amyloid beta accumulations at the intracellular level can cause an increase in the release of Ca2+ from the endoplasmic reticulum (ER). Calcium is a critical signaling molecule that is released in the form of puffs from intracellular stores such as the ER. The inositol 1,4,5-trisphosphate receptor (IP3R) is an ion channel that releases Ca2+.when activated by inositol trisphosphate (IP3). This is crucial for sustaining calcium levels in the cytosol. In this study, a simplified two-state model of the IP3R, which obtains predictions of Ca2+ levels in different parameters, was used to quantitatively reproduce statistics of calcium puffs in normal and AD-affected cells. This research applied the IP3R stochastic model which consequently investigated Ca2+ levels. We used results from the experimental data by using computational modeling to validate these changes and checked the alterations' effects on Ca2+ releases. Abnormalities in calcium regulation have been observed in several neurodegenerative diseases. We hope this research will contribute to the existing research on the causes of Alzheimer's disease and lead to a cure.