@article{5ff9a19d90ab46fab5a173e8117d973f,
title = "Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy",
abstract = "Accumulation of hyperphosphorylated tau directly correlates with cognitive decline in Alzheimer's disease and other primary tauopathies. One therapeutic strategy may be to reduce total tau expression. We identified antisense oligonucleotides (ASOs) that selectively decreased human taumRNA and protein inmice expressingmutant P301S human tau. After reduction of human tau in this mouse model of tauopathy, fewer tau inclusions developed, and preexisting phosphorylated tau and Thioflavin S pathology were reversed. The resolution of tau pathology was accompanied by the prevention of hippocampal volume loss, neuronal death, and nesting deficits. In addition, mouse survival was extended, and pathological tau seeding was reversed. In nonhuman primates, tau ASOs distributed throughout the brain and spinal cord and reduced taumRNA and protein in the brain, spinal cord, and cerebrospinal fluid. These data support investigation of a tau-lowering therapy in human patients who have tau-positive inclusions even after pathological tau deposition has begun. 2017",
author = "DeVos, {Sarah L.} and Miller, {Rebecca L.} and Schoch, {Kathleen M.} and Holmes, {Brandon B.} and Kebodeaux, {Carey S.} and Wegener, {Amy J.} and Guo Chen and Tao Shen and Hien Tran and Brandon Nichols and Zanardi, {Tom A.} and Kordasiewicz, {Holly B.} and Swayze, {Eric E.} and Bennett, {C. Frank} and Diamond, {Marc I.} and Miller, {Timothy M.}",
note = "Funding Information: This work was supported by the Tau Consortium (to M.I.D. and T.M.M.), the NIH [P50 AG05681 to T.M.M. (principal investigator, J.C. Morris), National Institute of Neurological Disorders and Stroke (NINDS) (R01NS078398 to T.M.M.), and National Institute on Aging (R21AG044719-01 to T.M.M.)], CurePSP (to T.M.M.), and a Paul B. Beeson Career Development Award (NINDS K08NS074194 to T.M.M.). The microscopy work was supported by the Hope Center Alafi Neuroimaging Laboratory and P30 Neuroscience Blueprint Interdisciplinary Center Core award to Washington University (P30 NS057105). Publisher Copyright: {\textcopyright} The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.",
year = "2017",
month = jan,
day = "25",
doi = "10.1126/scitranslmed.aag0481",
language = "English (US)",
volume = "9",
journal = "Science translational medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "374",
}