In a new paper published in Acta Neuropathologica Communications, a UCSF research team led by IND investigators Daniel Southworth and Carlo Condello used a novel combination of optical microscopy and cryogenic electron microscopy (cryo-EM) to study insoluble tau conformers in brain samples from individuals with Down syndrome (DS). High-resolution structures revealed paired helical filament and straight filament conformations of tau that were identical to those determined from the brains of individuals with Alzheimer's disease. These data provide the molecular framework required to identify conformation-specific diagnostic probes and to design novel therapeutic compounds targeting tau polymorphs found in DS.

Reference: Ghosh U, Tse E, Yang H, et al. Cryo-EM structures reveal tau filaments from Down syndrome adopt Alzheimer's disease fold. Acta Neuropathol Commun. 2024;12(1):94. Published 2024 Jun 12. doi:10.1186/s40478-024-01806-y