Rare bioactive tau oligomers from Alzheimer brain support both templated misfolding and fibril formation.

ABSTRACT: The accumulation of hyperphosphorylated tau aggregates is a hallmark of Alzheimer's disease (AD). In addition to long-recognized tau deposits in neurofibrillary tangles, recent studies suggest that diffusible, aqueous soluble (High Molecular Weight, or HMW) species are also bioactive, i.e., able to seed templated misfolding. The characteristics of the diffusible misfolded proteins are largely unknown, and their relationship to classical fibrillar structures is unclear. Using sequential size exclusion and anion exchange chromatography, we fractionated the HMW tau population and identified multiple subspecies varying in retention properties. The subspecies that elute early from the size column, and are retained on the anion exchange column are seed competent, whereas the other soluble fracti

SUBMITTER: Quittot N 

PROVIDER: S-EPMC12485776 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature