Alzheimer's disease (AD), a neurodegenerative "memory killer" demanding urgent global intervention, has long been shrouded in mystery regarding its core pathological mechanisms. Although the traditional amyloid-β (Aβ) hypothesis remains dominant, recent groundbreaking research has revealed that early activation of aberrant calcium (Ca⁺) signaling pathways serves as the "initiating trigger" of AD pathogenesis-preceding even the formation of classical Aβ plaques-a discovery that fundamentally overturns the existing cognitive framework. This study systematically deconstructs, for the first time, the cascading regulatory network of the Ca⁺/CaM-CaMKII signaling axis in AD pathology, elucidating its potential links with core AD mechanisms, including the Aβ hypothesis, tau hyperphosphorylation, Ca⁺ dyshomeostasis, synaptic dysfunction, and neuronal loss. Furthermore, this pathway not only triggers neurotoxic cascades through spatiotemporally specific regulation of synaptic Ca⁺ overload but also directly disrupts neuroplasticity-the physical basis of memory encoding-by reshaping the dynamic equilibrium between long-term potentiation (LTP) and long-term depression (LTD).Crucially, the research uncovers the dual role of CaMKII as a "molecular switch": while physiologically maintaining memory consolidation via Thr286 autophosphorylation, its pathological overactivation due to Ca⁺ dyshomeostasis leads to a "memory solidification-toxicity cycle." These findings establish a theoretical foundation for developing innovative therapies based on precise calcium signaling modulation-including Ca⁺ homeostasis intervention and CaMKII allosteric modulators-offering a potential breakthrough in overcoming the long-standing limitation of "symptom relief without targeting root causes" in AD treatment.