Amplification of Tau fibrils from minute quantities of seeds.
Amplification of Tau fibrils from minute quantities of seeds.
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DOI:
10.1021/bi501050g
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发表时间:
2014-09-16
期刊:
影响因子:
2.9
通讯作者:
Margittai, Martin
中科院分区:
文献类型:
--
作者:
Meyer, Virginia;Dinkel, Paul D.;Hager, Emily Rickman;Margittai, Martin
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.
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