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Am J Neurodegener Dis 2012;1(3):316-333

Original Article
Multiple mechanisms of extracellular tau spreading in a non-transgenic
tauopathy model

Meghan N Le, Wonhee Kim, Sangmook Lee, Ann C McKee, Garth F Hall

Department of Biological Sciences, University of Massachusetts Lowell, 198 Riverside Street Lowell MA, USA;
Alzheimer's Disease Research Laboratory, Department of Neuroscience, Tufts University School of Medicine, Boston,
MA, USA; 3Boston University Alzheimer’s Disease Center, Boston, MA 02118, USA.

Received November 9, 2012; Accepted November 21, 2012; Epub November 25, 2012; published November 30, 2012

Abstract: While the interneuronal propagation of neurofibrillary lesions in Alzheimer’s disease and other tauopathies
now appears to involve the spreading of tau-associated toxicity, little is known about its mechanism. We characterized
the movement of human tau through the brain of a non-transgenic lower vertebrate tauopathy model in which full-length
wild type and mutant human tau isoforms were expressed in identified neurons, thus permitting the identification and
localization of EC tau sources. We describe two distinct patterns of tau spreading that correspond to tau species that
lack (MTBR-) and contain (MTBR+) the tau microtubule-binding region. These patterns illustrate the production,
migration and uptake of EC tau and resemble some of the extracellular tau deposits typically seen in human brain after
repeated traumatic injury in cases of chronic traumatic encephalopathy (CTE). We propose that misprocessed human
tau can spread between CNS neurons via a variety of non-synaptic mechanisms as well as synaptically mediated
mechanisms. (AJND1211001).

Keywords: CSF-tau, tau secretion, neuron death, interneuronal lesion spread, chronic traumatic encephalopathy


Address all correspondence to:
Dr. Garth F Hall
Department of Biological Sciences
University of Massachusetts
Lowell198 Riverside Street Lowell MA, USA.
Phone: 978-934-2893, FAX 978 934 23044
E-mail: Garth_Hall@uml.edu