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Acta Neuropathol Commun. 2018 Aug 1;6(1):71. doi: 10.1186/s40478-018-0574-5.

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

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Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.
Mayo Clinic, Rochester, MN, USA.
Department of Pathology and Cell Biology, Taub Institute for Alzheimer's Disease Research, Columbia University Medical Center, New York, NY, USA.
University of Massachusetts Medical Center, Worcester, MA, USA.
Sanders-Brown Center on Aging, Department of Physiology, Spinal Cord and Brain Injury Research Center, and Epilepsy Center, University of Kentucky, Lexington, KY, USA.
Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.
Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Department of Pharmacology and Neurology Program in Neuroscience, Boston University School of Medicine, 72 East Concord St., R614, Boston, MA, 02118-2526, USA.


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.


Alzheimer’s disease; Immunohistochemistry; Mass spectrometry; Neurofibrillary tangle; Protein aggregation; Protein interactome

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