Crosstalk between calcium, amyloid beta and the receptor for advanced glycation endproducts in Alzheimer's disease.

Hallmarks of Alzheimer's disease (A beta) include the accumulation of amyloid beta peptide (A beta), hyperphosphorylation of tau protein, and increased inflammatory activity in the hippocampus and cerebral cortex. The receptor for advanced glycation endproducts; (RAGE) has been shown to interact with A beta and to modulate A beta transport across the blood-brain barrier. Furthermore, RAGE is upregulated at sites of inflammation and its activation results in distinct intracellular signaling cascades in respect to A beta conformers. Besides A beta, RAGE interacts with several members of the calcium binding S100 protein family, amphoterin and advanced glycation endproducts. Mounting evidence suggests that RAGE is a key player in the signaling pathways triggered by A beta and S100 proteins in A beta. In this review, we discuss recent discoveries about the crosstalk between RAGE, A beta and S100 proteins in the pathophysiology of A beta.