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01-01-2017 | Original Paper

Widespread tau seeding activity at early Braak stages

Authors: Jennifer L. Furman, Jaime Vaquer-Alicea, Charles L. White III, Nigel J. Cairns, Peter T. Nelson, Marc I. Diamond

Published in: Acta Neuropathologica | Issue 1/2017

Abstract

Transcellular propagation of tau aggregates may underlie the progression of pathology in Alzheimer’s disease (AD) and other tauopathies. Braak staging (B1, B2, B3) is based on phospho-tau accumulation within connected brain regions: entorhinal cortex (B1); hippocampus/limbic system (B2); and frontal and parietal lobes (B3). We previously developed a specific and sensitive assay that uses flow cytometry to quantify tissue seeding activity based on fluorescence resonance energy transfer (FRET) in cells that stably express tau reporter proteins. In a tauopathy mouse model, we have detected seeding activity far in advance of histopathological changes. It remains unknown whether individuals with AD also develop seeding activity prior to accumulation of phospho-tau. We measured tau seeding activity across four brain regions (hippocampus, frontal lobe, parietal lobe, and cerebellum) in 104 fresh-frozen human AD brain samples from all Braak stages. We observed widespread seeding activity, notably in regions predicted to be free of phospho-tau deposition, and in detergent-insoluble fractions that lacked tau detectable by ELISA. Seeding activity correlated positively with Braak stage and negatively with MMSE. Our results are consistent with early transcellular propagation of tau seeds that triggers subsequent development of neuropathology. The FRET-based seeding assay may also complement standard neuropathological classification of tauopathies.

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Title: Widespread tau seeding activity at early Braak stages
Authors: Jennifer L. Furman
Jaime Vaquer-Alicea
Charles L. White III
Nigel J. Cairns
Peter T. Nelson
Marc I. Diamond
Publication date: 01-01-2017
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 1/2017
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-016-1644-z

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Widespread tau seeding activity at early Braak stages

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