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International Journal of Cell Biology
Volume 2013, Article ID 260787, 9 pages
Research Article

Trimeric Tau Is Toxic to Human Neuronal Cells at Low Nanomolar Concentrations

1Department of Chemical Engineering, Arizona State University, P. O. Box 876106, Tempe, AZ 85287-6106, USA
2Oligomerix, Inc., 3960 Broadway, New York, NY 10032, USA

Received 14 May 2013; Revised 1 August 2013; Accepted 8 August 2013

Academic Editor: Alessio Cardinale

Copyright © 2013 Huilai Tian et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


In Alzheimer’s disease (AD), tau aggregates into fibrils and higher order neurofibrillary tangles, a key histopathological feature of AD. However, soluble oligomeric tau species may play a more critical role in AD progression since these tau species correlate better with neuronal loss and cognitive dysfunction. Recent studies show that extracellular oligomeric tau can inhibit memory formation and synaptic function and also transmit pathology to neighboring neurons. However, the specific forms of oligomeric tau involved in toxicity are still unknown. Here, we used two splice variants of recombinant human tau and generated monomeric, dimeric, and trimeric fractions of each isoform. The composition of each fraction was verified chromatographically and also by atomic force microscopy. The toxicity of each fraction toward both human neuroblastoma cells and cholinergic-like neurons was assessed. Trimeric, but not monomeric or dimeric, tau oligomers of both splice variants were neurotoxic at low nanomolar concentrations. Further characterization of tau oligomer species with disease-specific modifications and morphologies is necessary to identify the best targets for the development of biomarker and therapeutic development for AD and related tauopathies.