Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Although the
pathological hallmarks of AD have been identified, the derived therapies cannot effectively slow down
or stop disease progression; hence, it is likely that other pathogenic mechanisms are involved in AD
pathogenesis. Intracellular calcium (Ca2+) dyshomeostasis has been consistently observed in AD
patients and numerous AD models and may emerge prior to the development of amyloid plaques and
neurofibrillary tangles. Thus, intracellular Ca2+ disruptions are believed to play an important role in
AD development and could serve as promising therapeutic intervention targets.
One of the disrupted intracellular Ca2+ signaling pathways manifested in AD is attenuated storeoperated
Ca2+ entry (SOCE). SOCE is an extracellular Ca2+ entry mechanism mainly triggered by intracellular
Ca2+ store depletion. Maintaining normal SOCE function not only provides a means for the cell
to replenish ER Ca2+ stores but also serves as a cellular signal that maintains normal neuronal functions,
including excitability, neurogenesis, neurotransmission, synaptic plasticity, and gene expression.
However, normal SOCE function is diminished in AD, resulting in disrupted neuronal spine stability
and synaptic plasticity and the promotion of amyloidogenesis. Mounting evidence suggests that rectifying
diminished SOCE in neurons may intervene with the progression of AD. In this review, the
mechanisms of SOCE disruption and the associated pathogenic impacts on AD will be discussed. We
will also highlight the potential therapeutic targets or approaches that may help ameliorate SOCE deficits
for AD treatment.