On page 87, Yu et al. reveal that autophagic vesicles (AVs) are a breeding ground for the toxic β-amyloid peptide (Aβ). Prevention of abnormal AV accumulation might thus ward off Alzheimer's disease (AD).
Aβ had previously been localized to nebulous endocytic compartments. Based on evidence that AVs in liver contain the Aβ precursor, Yu et al. wondered whether autophagocytosis also creates Aβ. They found that isolated neuronal AVs contained Aβ and were highly enriched for the enzymes that create it. AVs were a major source of intracellular Aβ, which is increasingly thought to be more toxic than the secreted form.
Healthy brain tissue rarely contained AVs and thus accumulated little Aβ. But the authors found that neurons of brains in the early stages of AD, before neurodegeneration was apparent, contained unusually high numbers of AVs. These compartments normally fuse with degradative lysosomes, which might...
