Increased 4R-Tau Induces Pathological Changes in a Human-Tau Mouse Model.
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.
Schoch, KM; DeVos, SL; Miller, RL; Chun, SJ; Norrbom, M; Wozniak, DF; Dawson, HN; Bennett, CF; Rigo, F; Miller, TM
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