TY - JOUR
T1 - Increased 4R-Tau Induces Pathological Changes in a Human-Tau Mouse Model
AU - Schoch, Kathleen M M.
AU - DeVos, Sarah L L.
AU - Miller, Rebecca L L.
AU - Chun, Seung J J.
AU - Norrbom, Michaela
AU - Wozniak, David F F.
AU - Dawson, Hana N N.
AU - Bennett, C. Frank
AU - Rigo, Frank
AU - Miller, Timothy M M.
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84975519193&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2016.04.042
DO - 10.1016/j.neuron.2016.04.042
M3 - Article
C2 - 27210553
AN - SCOPUS:84975519193
SN - 0896-6273
VL - 90
SP - 941
EP - 947
JO - Neuron
JF - Neuron
IS - 5
ER -