Figure 6.

Mechanisms of ER Ca²⁺ dyshomeostasis in Alzheimer’s disease (AD). Mutated presenilin (PS) increases ER Ca²⁺ release. Various models of AD display increased expression of RyR, which can also produce elevated Ca²⁺ release from the ER. Additionally, mutated PS stimulates sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA), which can fuel further release through ER Ca²⁺ channels. Increased ER Ca²⁺ store depletion can activate store operated Ca²⁺ entry. Function of mitochondria associated membranes (MAMs) are also altered by mutated PS.