Trimeric tau is toxic to human neuronal cells at low nanomolar concentrations

Huilai Tian, Eliot Davidowitz, Patricia Lopez, Sharareh Emadi, James Moe, Michael Sierks

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number260787
JournalInternational Journal of Cell Biology
DOIs
StatePublished - 2013

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Poisons
Alzheimer Disease
Tauopathies
Neurofibrillary Tangles
Cholinergic Neurons
Atomic Force Microscopy
Neuroblastoma
Disease Progression
Protein Isoforms
Biomarkers
Pathology
Neurons
Therapeutics

ASJC Scopus subject areas

  • Cell Biology

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Trimeric tau is toxic to human neuronal cells at low nanomolar concentrations. / Tian, Huilai; Davidowitz, Eliot; Lopez, Patricia; Emadi, Sharareh; Moe, James; Sierks, Michael.

In: International Journal of Cell Biology, 2013.

Research output: Contribution to journalArticle

Tian, Huilai ; Davidowitz, Eliot ; Lopez, Patricia ; Emadi, Sharareh ; Moe, James ; Sierks, Michael. / Trimeric tau is toxic to human neuronal cells at low nanomolar concentrations. In: International Journal of Cell Biology. 2013.
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