Close encounter: mitochondria, endoplasmic reticulum and Alzheimer's disease

Alzheimer's disease (AD) is characterized by the loss of hippocampal and cortical neurons as a consequence of the accumulation of amyloid-beta (A beta). A beta is produced from the amyloid precursor protein (APP) by the gamma-secretase complex components presenilin-1 (PS1) and -2 (PS2), which are mutated in genetic forms of AD. In this issue, Schon and coworkers show that PS1 and PS2 are located at the interface between mitochondria and endoplasmic reticulum (ER). In models of familial and sporadic AD, these two organelles are juxtaposed closely, affecting shared lipid metabolic pathways. The interface between mitochondria and ER emerges as a new potential determinant of AD pathogenesis.