EDITOR'S CHOICE IN NEUROSCIENCE
Z. Zhang et al., “Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer’s disease,” Nature Medicine, 20:1254-62, 2014.
Tangles of truncated tau proteins squished inside brain cells are a hallmark of Alzheimer’s disease (AD), though their precise origins are mysterious. Aging, the strongest risk factor for AD, is linked to a drop in neurons’ pH, hinting that acidosis might influence tau fragmentation. In 2008, Keqiang Ye of Emory University and colleagues discovered that at a pH of 6.0, a lysosomal enzyme called asparagine endopeptidase (AEP) moved into the cytoplasm and cleaved brain proteins. This led them to explore whether AEP also acted on tau.
Assays of mouse and human brains confirmed...