(300 WORDS MAX) Two proteins called amyloid-beta tau are both strongly implicated in the etiology of Alzheimer's disease. Amyloid-beta has been by far the major focus in AD drug discovery. Although tau is also an essential component in the etiology of Alzheimer's disease, its role in this process is not understood, and tau is very underdeveloped as a therapeutic target. Major clues to its role are over 40 mutations in the tau gene that cause Alzheimer-related dementias. Many of these mutations alter the splicing of the tau messenger RNA (mRNA, the intermediate between gene and protein) and thereby shift the balance between two types of tau proteins (called 3R and 4R tau). We have recently validated a postulated hairpin motif in the tau mRNA as a bona fide structure that regulates 3R vs. 4R tau formation in cells. We have also carried out a high-throughput screen to identify small drug-like compounds that bind to and stabilize this hairpin structure as a potential therapeutic strategy. In addition, we have identified a novel strategy to stabilize the hairpin by interaction with regions that flank this structure. Our overarching goal is to combine these two strategies to develop potent "molecular clasps" to fix the hairpin structure of tau mRNA in a highly targeted manner, that is, highly selective over the many other RNA molecules in a cell.