Knockdown of amyloid precursor protein increases calcium levels in the endoplasmic reticulum.

Familial Alzheimer's disease (AD) is caused by mutations in the genes that encode amyloid precursor protein (APP) and presenilins. Disturbances in calcium homeostasis have been observed in various cellular and animal models of AD and are proposed to underlie the pathogenesis of the disease. Furthermore, wildtype presenilins were shown to regulate endoplasmic reticulum (ER) calcium homeostasis, although their precise mechanism of action remains controversial.

[Microscopic imaging of calcium ions with genetically encoded calcium indicators].

Calcium is a second messenger that plays a key role in various cellular processes. Monitoring calcium levels is a prerequisite to their understanding. The first calcium indicators for microscopy were the luminescent protein aequorin and chemical probes.

Microscopic analysis of Orai-mediated store-operated calcium entry in cells with experimentally altered levels of amyloid precursor protein.

Familial Alzheimer's disease (FAD)-causing mutations in presenilins were shown to alter intracellular calcium dynamics, including store-operated calcium entry (SOCE). However, the involvement of FAD-linked amyloid precursor protein (APP) in SOCE remains controversial. Here, we used gain-of-function and loss-of-function approaches to shed light on this issue.