4-Repeat tau seeds and templating subtypes as brain and CSF biomarkers of frontotemporal lobar degeneration.

ABSTRACT: To address the need for more meaningful biomarkers of tauopathies, we have developed an ultrasensitive tau seed amplification assay (4R RT-QuIC) for the 4-repeat (4R) tau aggregates of progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and other diseases with 4R tauopathy. The assay detected seeds in 10⁶-10⁹-fold dilutions of 4R tauopathy brain tissue but was orders of magnitude less responsive to brain with other types of tauopathy, such as from Alzheimer's disease cases. The analytical sensitivity for synthetic 4R tau fibrils was ~ 50 fM or 2 fg/sample. A novel dimension of this tau RT-QuIC testing was the identification of three disease-associated classes of 4R tau seeds; these classes were revealed by conformational variations in the in vitro a

SUBMITTER: Saijo E 

PROVIDER: S-EPMC7192393 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature