Amplification of Tau Fibrils from Minute Quantities of Seeds | Zendy

Virginia Meyer | Zendy; Paul D. Dinkel | Zendy; Emily R. Hager | Zendy; Martin Margittai | Zendy

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Amplification of Tau Fibrils from Minute Quantities of Seeds

Author(s) -

Virginia Meyer,

Paul D. Dinkel,

Emily R. Hager,

Martin Margittai

Publication year - 2014

Publication title -

biochemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.43

H-Index - 253

eISSN - 1520-4995

pISSN - 0006-2960

DOI - 10.1021/bi501050g

Subject(s) - fibril , nucleation , chemistry , biophysics , tau protein , amyloid fibril , shearing (physics) , biochemistry , alzheimer's disease , amyloid β , materials science , biology , disease , organic chemistry , pathology , composite material , medicine

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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