CALR and Alzheimer disease: Ablation of calreticulin, reduction of calreticulin levels or interference with calreticulin's binding to APP enables APP to interact directly with presenilin and the other components of the γ-secretase complex (Fig. 10D) leading to increased proteolytic cleavage of APP, to enhanced Aβ production and to aggregation of Aβ, contributing to the amyloidogenic aspect of AD pathology.