Identification of Novel Tau Interactions with Endoplasmic Reticulum Proteins in Alzheimer's Disease Brain

Shelby Meier, Michelle Bell, Danielle N. Lyons, Alexandria Ingram, Jing Chen, John C. Gensel, Haining Zhu, Peter T. Nelson, Jose F. Abisambra

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is pathologically characterized by the formation of extracellular amyloid plaques and intraneuronal tau tangles. We recently identified that tau associates with proteins known to participate in endoplasmic reticulum (ER)-associated degradation (ERAD); consequently, ERAD becomes dysfunctional and causes neurotoxicity. We hypothesized that tau associates with other ER proteins, and that this association could also lead to cellular dysfunction in AD. Portions of human AD and non-demented age matched control brains were fractionated to obtain microsomes, from which tau was co-immunoprecipitated. Samples from both conditions containing tau and its associated proteins were analyzed by mass spectrometry. In total, we identified 91 ER proteins that co-immunoprecipitated with tau; 15.4 were common between AD and control brains, and 42.9 only in the AD samples. The remainder, 41.8 of the proteins, was only seen in the control brain samples. We identified a variety of previously unreported interactions between tau and ER proteins. These proteins participate in over sixteen functional categories, the most abundant being involved in RNA translation. We then determined that association of tau with these ER proteins was different between the AD and control samples. We found that tau associated equally with the ribosomal protein L28 but more robustly with the ribosomal protein P0. These data suggest that the differential association between tau and ER proteins in disease could reveal the pathogenic processes by which tau induces cellular dysfunction.

Original languageEnglish (US)
Pages (from-to)687-702
Number of pages16
JournalJournal of Alzheimer's Disease
Volume48
Issue number3
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Keywords

  • Alzheimer's disease
  • co-immunoprecipitation
  • endoplasmic reticulum
  • mass spectrometry
  • microsome
  • ribosome
  • tau
  • tauopathies

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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