title: Amplification of Tau fibrils from minute quantities of seeds.
abstract: The propagation of Tau pathology in Alzheimer's disease (AD) is thought to proceed through templated conversion of Tau protein into fibrils and cell-to-cell transfer of elongation-competent seeds. To investigate the efficiency of Tau conversion, we adapted the protein misfolding cyclic amplification assay used for the conversion of prions. Utilizing heparin as a cofactor and employing repetitive cycles of shearing and growth, synthetic Tau fibrils and Tau fibrils in AD brain extract are progressively amplified. Concurrently, self-nucleation is suppressed. The results highlight breakage-induced replication of Tau fibrils as a potential facilitator of disease spread.
authors.affiliation: Department of Chemistry and Biochemistry, University of Denver , Denver, Colorado 80208, United States.
authors.forename: Virginia
authors.initials: V
authors.lastname: Meyer
authors.forename: Paul D
authors.initials: PD
authors.lastname: Dinkel
authors.forename: Emily
authors.initials: E
authors.lastname: Rickman Hager
authors.forename: Martin
authors.initials: M
authors.lastname: Margittai
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism; D006493:Heparin / Q000737:chemistry; D006801:Humans; D008854:Microscopy, Electron; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D016875:tau Proteins; D006493:Heparin