{Reference Type}: Preprint
{Title}: Cryo-EM structure of Alzheimer's disease tau filaments with PET ligand MK-6240.
{Author}: Kunach P;Vaquer-Alicea J;Smith MS;Hopewell R;Monistrol J;Moquin L;Therriault J;Tissot C;Rahmouni N;Massarweh G;Soucy JP;Guiot MC;Shoichet BK;Rosa-Neto P;Diamond MI;Shahmoradian SH;
{Journal}: bioRxiv
{Volume}: 0
{Issue}: 0
{Year}: 2023 Sep 22
暂无{DOI}: 10.1101/2023.09.22.558671
{Abstract}: Positron Emission Tomography (PET) ligands have advanced Alzheimer's disease (AD) diagnosis and treatment. Using autoradiography and cryo-EM, we identified AD brain tissue with elevated tau burden, purified filaments, and determined the structure of second-generation high avidity PET ligand MK-6240 at 2.31 Å resolution, which bound at a 1:1 ratio within the cleft of tau paired-helical filament (PHF), engaging with glutamine 351, lysine K353, and isoleucine 360. This information elucidates the basis of MK-6240 PET in quantifying PHF deposits in AD and may facilitate the structure-based design of superior ligands against tau amyloids.