Calcium signaling dysregulation and neurodegeneration in Alzheimer’s disease

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by cognitive decline, synaptic dysfunction, and widespread neuronal vulnerability. While Alzheimer’s pathology is commonly discussed in the context of amyloid and tau, growing evidence indicates that disrupted calcium homeostasis and abnormal intracellular calcium signaling may represent a convergent mechanism that links multiple downstream processes in disease progression.

Neurons rely on tightly regulated calcium dynamics to maintain synaptic transmission, mitochondrial energy balance, gene expression, and long term plasticity. Under physiological conditions, calcium signals are transient, compartmentalized, and precisely buffered. In Alzheimer’s disease, these control systems may become destabilized, leading to persistent calcium stress that amplifies oxidative injury, metabolic dysfunction, and inflammatory signaling. Over time, calcium signaling imbalance may contribute to synaptic loss, impaired network function, and reduced neuronal resilience.

Importantly, calcium signaling disruption is not limited to a single pathway. It can involve altered calcium entry, abnormal release from intracellular stores, impaired calcium extrusion, and receptor level dysregulation. These changes may interact with disease associated protein aggregation, vascular impairment, and neuroimmune activation, forming a self reinforcing cycle that accelerates neurodegeneration.

At CBHI, our Alzheimer’s research content focuses on mechanistic clarity. We summarize current evidence on how calcium signaling may go wrong in the aging brain, how this relates to established Alzheimer’s pathology, and what therapeutic strategies are being explored to restore calcium balance and protect neuronal function.