Increased 4R-Tau Induces Pathological Changes in a Human-Tau Mouse Model.


Journal Article

Pathological evidence for selective four-repeat (4R) tau deposition in certain dementias and exon 10-positioned MAPT mutations together suggest a 4R-specific role in causing disease. However, direct assessments of 4R toxicity have not yet been accomplished in vivo. Increasing 4R-tau expression without change to total tau in human tau-expressing mice induced more severe seizures and nesting behavior abnormality, increased tau phosphorylation, and produced a shift toward oligomeric tau. Exon 10 skipping could also be accomplished in vivo, providing support for a 4R-tau targeted approach to target 4R-tau toxicity and, in cases of primary MAPT mutation, eliminate the disease-causing mutation.

Full Text

Cited Authors

  • Schoch, KM; DeVos, SL; Miller, RL; Chun, SJ; Norrbom, M; Wozniak, DF; Dawson, HN; Bennett, CF; Rigo, F; Miller, TM

Published Date

  • June 2016

Published In

Volume / Issue

  • 90 / 5

Start / End Page

  • 941 - 947

PubMed ID

  • 27210553

Pubmed Central ID

  • 27210553

Electronic International Standard Serial Number (EISSN)

  • 1097-4199

International Standard Serial Number (ISSN)

  • 0896-6273

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2016.04.042


  • eng