Finding the dark side of tau

On page 1051, Stamer et al. have uncovered what may be a critical early step in the pathogenesis of Alzheimer's disease and a previously unappreciated regulatory system for microtubule-based motors. The work focuses on the microtubule-associated protein tau, which is thought to cause the pathological changes seen in some neurodegenerative diseases. The prevailing view is that tau stabilizes microtubules, and disease results when the protein detaches from microtubules and aggregates into paired helical filaments. According to the authors, the opposite situation—having too much tau attached to microtubules—may be just as bad.

Overexpressing tau in neuroblastoma cell lines, primary hippocampal neurons, or retinal ganglion cells leaves microtubules intact. Rather than forming filaments, the overexpressed tau binds to microtubules and appears to lay the groundwork for neurodegeneration. Excess tau causes the depletion of mitochondria and peroxisomes...