Translation Initiation of the Human Tau mRNA Through an Internal Ribosomal Entry Site

Neurofibrillary tangles are a pathological phenotype in Alzheimer's disease (AD) and are caused by the hyperphospho- rylation of the microtubule associated protein tau. In mouse models of AD, decreasing tau protein expression limits the severity of symptoms and inhibits progression of AD. We now report that the 5' leader in the human tau mRNA contains an internal ribosomal entry site (IRES) and that IRES-dependent translation plays a role in the synthesis of tau protein. Consequently, targeting the tau IRES provides a novel target for regulating tau expression in AD and other tauopathies.