[PDF][PDF] Increased 4R-tau induces pathological changes in a human-tau mouse model

KM Schoch, SL DeVos, RL Miller, SJ Chun, M Norrbom… - Neuron, 2016 - cell.com
KM Schoch, SL DeVos, RL Miller, SJ Chun, M Norrbom, DF Wozniak, HN Dawson…
Neuron, 2016cell.com
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 …
Summary
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.
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