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

Kathleen M M. Schoch, Sarah L L. DeVos, Rebecca L L. Miller, Seung J J. Chun, Michaela Norrbom, David F F. Wozniak, Hana N N. Dawson, C.  Frank Bennett, Frank Rigo, Timothy M M. Miller

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)941-947
Number of pages7
JournalNeuron
Volume90
Issue number5
DOIs
StatePublished - Jun 1 2016

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