I recommend this paper
The prominence of early/pre-symptomatic calcium signaling disruptions in mutant presenilin (PS)-expressing neurons has been well established in the AD field, but to fortify relevance to the disease process, dysregulated calcium still needs to be transduced into a pathogenic mechanism. This study by Müller et al. is very effective at demonstrating how increased ER calcium release, via the IP3R, results in constitutive upregulation of a calcium-regulated kinase and gene transcription pathway.
Normally, CaMKIV and pCREB activation are associated with neuronal functionality and plasticity, and are recruited in a specific and activity-dependent manner. However, with mutant PS expression, this signaling cascade and associated immediate early genes are continuously engaged. While there are many long-term negative effects that can stem from this homeostasis shift (such as the demonstrated increased vulnerability to cell death and amyloid toxicity), the specific links to AD pathology are still to be determined.
We know that at early disease stages, prior to the onset of amyloid...