We have hypothesized that an intracellular calcium deficit may occur in the early phase of Alzheimer's disease (AD). This hypothesis has two important corollaries. First, it predicts that elevation of calcium levels by many calcium agonists, in principle, would have protective effects in the individuals at-risk to AD. Second, it implies that an artificial decrease of the calcium levels by the use of calcium antagonists might mimic the AD pathologies in the experimental animals. Obviously, the latter prediction not only would allow a direct testing of the hypothesis, but also might offer a "new" route for developing an animal model for sporadic AD. In fact, a number of the existing models that target various neurotransmitter receptors and calcium channels has manifested memory deficits. This suggests that a fully successful animal model for AD might be developed by improving the current paradigms. Furthermore, we discuss a potential relationship between AD and schizophrenia in terms of intracellular calcium imbalance.