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Amplification of Tau Fibrils from Minute Quantities of Seeds

By Virginia Meyer, Paul D. Dinkel, Emily Rickman Hager and Martin Margittai


ABSTRACT: The propagation of Tau pathology in Alz-heimer’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. Tau fibrils, deposited in the interior of nerve cells, are adefining hallmark of Alzheimer’s disease (AD) and other fatal neurodegenerative disorders.1,2 Fibrillar Tau species can transfer between cells and then recruit endogenous Ta

Year: 2016
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