Alzheimer's disease (AD) is the threat of modern humankind that is provoked by increased human lifespan. Despite extensive studies on AD pathology for more than 100 years, there are no disease-preventing therapies. Growing evidence suggests the role of calcium (Ca2+) in the pathogenesis of AD. The main purpose of the article is to understand whether modern science is able to explain the synapse loss observed in early AD and discuss the role of Ca2+ hypothesis in it. Based on results obtained in our laboratory and others, we propose that familial AD-associated mutations in presenilins cause a Ca2+ overload of endoplasmic reticulum stores which leads to compensatory downregulation of the neuronal store-operated Ca2+ (nSOC) entry pathway. We propose that synaptic nSOC is necessary for the stability of mature synaptic spines and that dysfunction of this pathway may play an important role in synaptic and memory loss in AD.

Keywords:
Alzheimer’s disease, Calcium signaling, Synapse, Mushroom spines, Neuronal store-operated channels
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© 2013 S. Karger AG, Basel
2013
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