Background: The interactions between Alzheimer’s Disease (AD) and major depression
can be translated into clinical data showing that depressive patients have had an enhanced risk for
developing AD (later in life). The cellular mechanisms involved in these interactions remain under
intensive debate in the literature. In addition, the role of a Ca2+ homeostasis dysregulation in the
pathogenesis of neurodegenerative diseases, like AD, and major depression has been under intensive
Objective: Thus, revealing the interplay between AD and major depression may provide novel insights
into the pathogenesis of these diseases.
Methods: Publications involving Ca2+ signalling pathways, AD, and major depression (alone or
combined) were collected by searching multiple databases to find the maximum number of relevant
citations (using a search strategy with high sensitivity for studies of etiology).
Results: Ca2+ Channel Blockers (CCBs), classically prescribed for hypertensive patients, have been
demonstrating neuroprotective effects, such as decreasing the incidence of AD in hypertensive patients,
including alleviating major depression symptoms. A mechanism under debate is focused on the restoration
of the Ca2+ homeostasis. Indeed, previous studies of our own have correlated Ca2+ and cAMP signalling
pathways (Ca2+/cAMP signalling) in controlling both the neurotransmitter release and neuronal
death. These studies also observed that CCBs can affect Ca2+/cAMP signalling.
Conclusion: This review discussed the plausible role of Ca2+/cAMP signalling in the neuroprotective
effects of CCBs, including the participation of Ca2+/cAMP signalling in the interactions between
major depression and AD. Considering both AD and major depression have become highly
prevalent medical problems in the world, the comprehension of the interactions between these diseases
could improve drug development.