Tau-Mediated RNA Splicing Errors Linked to Alzheimer's Disease

A study in Cell Reports demonstrates a new molecular cause for neurodegeneration in Alzheimer's, reports Medical Xpress . The research unveiled a unique mechanism common to alterations in RNA splicing and tau-mediated neurodegeneration in Alzheimer's. RNA splicing plays a role in the production of mature RNA molecules for generating functional proteins, and the researchers explored the possibility that aggregates of tau protein within neurons disrupt this process. The team first overexpressed toxic tau in fruit flies to test whether spliceosome-tau interactions might induce neurodegeneration. The implication was that tau aggregates either interfered with proper assembly of the spliceosome or contained key components in the cytoplasm, away from the site of action in the nucleus. Experiments in which flies expressing toxic tau had global disruptions in RNA splicing that led to thousands of erroneous RNAs further supported this hypothesis. "Our findings present an exciting new possibility of using RNA splicing as a potential molecular target for Alzheimer's disease and other tau-mediated neurodegenerative conditions," said Baylor College of Medicine Professor Joshua Shulman.