Pathological tau promotes neuronal damage by impairing ribosomal function and decreasing protein synthesis

Shelby Meier, Michelle Bell, Danielle N. Lyons, Jennifer Rodriguez-Rivera, Alexandria Ingram, Sarah N. Fontaine, Elizabeth Mechas, Jing Chen, Benjamin Wolozin, Harry Le Vine, Haining Zhu, Jose F. Abisambra

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

One of the most common symptoms of Alzheimer’s disease (AD) and related tauopathies is memory loss. The exact mechanisms leading to memory loss in tauopathies are not yet known; however, decreased translation due to ribosomal dysfunction has been implicated as a part of this process. Here we use a proteomics approach that incorporates subcellular fractionation and coimmunoprecipitation of tau from human AD and non-demented control brains to identify novel interactions between tau and the endoplasmic reticulum (ER). We show that ribosomes associate more closely with tau in AD than with tau in control brains, and that this abnormal association leads to a decrease in RNA translation. The aberrant tau-ribosome association also impaired synthesis of the synaptic protein PSD-95, suggesting that this phenomenon contributes to synaptic dysfunction. These findings provide novel information about tau-protein interactions in human brains, and they describe, for the first time, a dysfunctional consequence of tau-ribosome associations that directly alters protein synthesis.

Original languageEnglish (US)
Pages (from-to)957-962
Number of pages6
JournalJournal of Neuroscience
Volume36
Issue number3
DOIs
StatePublished - Jan 20 2016
Externally publishedYes

Keywords

  • Alzheimer
  • Ribosome
  • RNA
  • Tau
  • Tauopathies
  • Translation

ASJC Scopus subject areas

  • Neuroscience(all)

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