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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.

SUBMITTER: Meyer V

PROVIDER: S-EPMC4165214 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Amplification of Tau fibrils from minute quantities of seeds.

Meyer Virginia V Dinkel Paul D PD Rickman Hager Emily E Margittai Martin M

Biochemistry 20140829 36

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 progress ...[more]

PMID: 25153692

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