APP and Alzheimer disease: Together, all these observations not only support the concept that MAMs emerge as intracellular sites for amyloidogenic APP processing, but also that MAM agglutinates several other biochemical and morphological features typically observed at early stages of AD (Figure 2B), especially mitochondrial dysfunction as a common feature in many neurodegenerative diseases, defining the so called MAM hypothesis as a key event for AD pathogenesis (Area-Gomez and Schon, 2017).