The article discusses the role of neuronal calcium homeostasis in the pathogenesis of Alzheimer's disease (AD). It highlights how age-related oxidative stress and impaired energy metabolism compromise the function of proteins that control membrane excitability and subcellular calcium dynamics. Toxic forms of amyloid β-peptide (Aβ) can induce calcium influx into neurons by forming pores in the membrane or by inducing membrane-associated oxidative stress, making neurons vulnerable to excitotoxicity and apoptosis. Mutations in the β-amyloid precursor protein and presenilins can disrupt normal protein functions in the plasma membrane and endoplasmic reticulum, respectively. The article also explores the potential of novel preventative and therapeutic interventions based on emerging knowledge of calcium signaling upstream and downstream of Aβ. Additionally, it examines the adverse effects of aging on neuronal calcium signaling, the mechanisms by which Aβ promotes calcium influx and excitotoxicity, and the role of presenilins in modulating calcium homeostasis. The article concludes by discussing the importance of optimizing neuronal calcium homeostasis as a therapeutic approach for AD and the potential of specific calcium-regulating mechanisms as targets for therapeutic intervention.The article discusses the role of neuronal calcium homeostasis in the pathogenesis of Alzheimer's disease (AD). It highlights how age-related oxidative stress and impaired energy metabolism compromise the function of proteins that control membrane excitability and subcellular calcium dynamics. Toxic forms of amyloid β-peptide (Aβ) can induce calcium influx into neurons by forming pores in the membrane or by inducing membrane-associated oxidative stress, making neurons vulnerable to excitotoxicity and apoptosis. Mutations in the β-amyloid precursor protein and presenilins can disrupt normal protein functions in the plasma membrane and endoplasmic reticulum, respectively. The article also explores the potential of novel preventative and therapeutic interventions based on emerging knowledge of calcium signaling upstream and downstream of Aβ. Additionally, it examines the adverse effects of aging on neuronal calcium signaling, the mechanisms by which Aβ promotes calcium influx and excitotoxicity, and the role of presenilins in modulating calcium homeostasis. The article concludes by discussing the importance of optimizing neuronal calcium homeostasis as a therapeutic approach for AD and the potential of specific calcium-regulating mechanisms as targets for therapeutic intervention.