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Open Access 01-12-2018 | Research

RNA binding proteins co-localize with small tau inclusions in tauopathy

Authors: Brandon F. Maziuk, Daniel J. Apicco, Anna Lourdes Cruz, Lulu Jiang, Peter E. A. Ash, Edroaldo Lummertz da Rocha, Cheng Zhang, Wai Haung Yu, John Leszyk, Jose F. Abisambra, Hu Li, Benjamin Wolozin

Published in: Acta Neuropathologica Communications | Issue 1/2018

Abstract

The development of insoluble, intracellular neurofibrillary tangles composed of the microtubule-associated protein tau is a defining feature of tauopathies, including Alzheimer’s disease (AD). Accumulating evidence suggests that tau pathology co-localizes with RNA binding proteins (RBPs) that are known markers for stress granules (SGs). Here we used proteomics to determine how the network of tau binding proteins changes with disease in the rTg4510 mouse, and then followed up with immunohistochemistry to identify RNA binding proteins that co-localize with tau pathology. The tau interactome networks revealed striking disease-related changes in interactions between tau and a multiple RBPs, and biochemical fractionation studies demonstrated that many of these proteins including hnRNPA0, EWSR1, PABP and RPL7 form insoluble aggregates as tau pathology develops. Immunohistochemical analysis of mouse and human brain tissues suggest a model of evolving pathological interaction, in which RBPs co-localize with pathological phospho-tau but occur adjacent to larger pathological tau inclusions. We suggest a model in which tau initially interacts with RBPs in small complexes, but evolves into isolated aggregated inclusions as tau pathology matures.

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Title: RNA binding proteins co-localize with small tau inclusions in tauopathy
Authors: Brandon F. Maziuk
Daniel J. Apicco
Anna Lourdes Cruz
Lulu Jiang
Peter E. A. Ash
Edroaldo Lummertz da Rocha
Cheng Zhang
Wai Haung Yu
John Leszyk
Jose F. Abisambra
Hu Li
Benjamin Wolozin
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2018
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-018-0574-5

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RNA binding proteins co-localize with small tau inclusions in tauopathy

Abstract

Keynote webinar | Spotlight on medication adherence

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Abstract

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