Figure 1.

FAD (familial Alzheimer’s disease) presenilin mutations result in enhanced ER (endoplasmic reticulum) calcium release. Under pathological condition associated with FAD, there is excessive ER (calcium release) as a result of overexpression of RYR (ryanodine receptors) and potentiation of IP₃R (IP₃ receptors). Also, hyperactivity of SERCA (sarco/endoplasmic reticulum calcium ATPase) pumps and the loss of leak channel function of PSEN (presenilin) can increase ER-calcium stores thereby increasing release of calcium via RYR and IP₃R. Black arrows indicate direction of calcium movement.