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Published in: Acta Neuropathologica Communications 1/2019

Open Access 01-12-2019 | Alzheimer's Disease | Research

Tau exhibits unique seeding properties in globular glial tauopathy

Authors: Dah-eun Chloe Chung, Yari Carlomagno, Casey N. Cook, Karen Jansen-West, Lillian Daughrity, Laura J. Lewis-Tuffin, Monica Castanedes-Casey, Michael DeTure, Dennis W. Dickson, Leonard Petrucelli

Published in: Acta Neuropathologica Communications | Issue 1/2019

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Abstract

Tauopathies are neurodegenerative disorders characterized by aggregation of microtubule associated tau protein in neurons and glia. They are clinically and pathologically heterogeneous depending on the isoform of tau protein that accumulates (three or four 31-to-32-amino-acid repeats [3R or 4R] in the microtubule binding domain), as well as the cellular and neuroanatomical distribution of tau pathology. Growing evidence suggests that distinct tau conformers may contribute to the characteristic features of various tauopathies. Globular glial tauopathy (GGT) is a rare 4R tauopathy with globular cytoplasmic inclusions within neurons and glial cells. Given the unique cellular distribution and morphology of tau pathology in GGT, we sought to determine if tau species in GGT had distinctive biological properties. To address this question, we performed seeding analyses with postmortem brain tissues using a commercial tau biosensor cell line. We found that brain lysates from GGT cases had significantly higher seeding competency than other tauopathies, including corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD). The robust seeding activity of GGT brain lysates was independent of phosphorylated tau burden and diminished upon removal of tau from samples, suggesting that seeding properties were indeed mediated by tau in the lysates. In addition, cellular inclusions in the tau biosensor cell line induced by GGT had a distinct, globular morphology that was markedly different from inclusions induced by other tauopathies, further highlighting the unique nature of tau species in GGT. Characterization of different tau species in GGT showed that detergent-insoluble, fibril-like tau contained the highest seeding activity, as reflected in its ability to increase tau aggregation in primary glial cultures. Taken together, our data suggest that unique seeding properties differentiate GGT-tau from other tauopathies, which provides new insight into pathogenic heterogeneity of primary neurodegenerative tauopathies.
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Metadata
Title
Tau exhibits unique seeding properties in globular glial tauopathy
Authors
Dah-eun Chloe Chung
Yari Carlomagno
Casey N. Cook
Karen Jansen-West
Lillian Daughrity
Laura J. Lewis-Tuffin
Monica Castanedes-Casey
Michael DeTure
Dennis W. Dickson
Leonard Petrucelli
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2019
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/s40478-019-0691-9

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