Generating paired helical filaments (PHFs) in vitro presents new opportunities for Alzheimer’s research

Research spearheaded by Sofia Lövestam in Michel Goedert and Sjors Scheres’ groups has identified a combination of 12 residues in tau which, when mutated in vitro, prompt the formation of paired helical filaments (PHFs), the distinctive hallmark of advanced Alzheimer’s disease. Interestingly, in the engineered tau, named PAD12, the residues in question are all outside of tau’s fibril core, found instead in the fuzzy coat. This significant breakthrough is the first successful in vitro attempt to generate PHFs which match brain-derived structures, shedding light on their formation and revealing a powerful new model for investigating tau pathology. More…