Figure 4.

Dysregulation of Ca²⁺ and redox signalling in Alzheimer's disease (AD). The calcium hypothesis of AD suggests that the formation of Aβ oligomers brings about an overall increase in Ca²⁺ signalling that results in a permanent elevation in the resting level of Ca²⁺ to 300 nM that then erases memories soon after they are formed by activating calcineurin (CaN) inducing long-term depression (LTD). An elevation of Ca²⁺ sets up a positive feedback loop by acting to stimulate the hydrolysis of the amyloid precursor protein (APP) to generate the Aβ oligomers that bind to the cellular prion protein (PrP^C) that then activates the InsP₃/Ca²⁺ signalling pathway. Vitamin D reduces the risk of AD by acting to maintain Ca²⁺ and redox signalling at their normal low resting levels.