查看文章

Alzheimer disease (AD) is a debilitating neurodegenerative disorder characterized by extracellular deposition of the amyloid β-protein (Aβ) and intraneuronal accumulation of the microtubule-associated protein, tau. Despite a wealth of experimental and genetic evidence implicating both Aβ and tau in the pathogenesis of AD, the precise molecular links between these two pathological hallmarks have remained surprisingly elusive. Here, we review emerging evidence for a critical nexus among Aβ, tau, and the lysosomal protease cathepsin D (CatD) that we hypothesize may play a pivotal role in the etiology of AD. CatD degrades both Aβ and tau in vitro, but the in vivo relevance of this lysosomal protease to these principally extracellular and cytosolic proteins, respectively, had remained undefined for many decades. Recently, however, our group found that genetic deletion of CatD in mice results in dramatic …