caa a22 4500 528786385 20190713030957.0 cr unu---uuuuu 180924s2015 xx s 000 0 eng 10.3929/ethz-b-000105367 doi 10.1038/ncomms9490 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/105367 Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain [Elektronische Daten] [Shuko Takeda, Susanne Wegmann, Hansang Cho, Sarah L. DeVos, Caitlin Commins, Allyson D. Roe, Samantha B. Nicholls, George A. Carlson, Rose Pitstick, Chloe K. Nobuhara, Isabel Costantino, Matthew P. Frosch, Daniel J.; id_orcid 0000-0003-3075-0665 Müller, Daniel Irimia, Bradley T. Hyman] Nat Commun Open access ethresearch Tau pathology is known to spread in a hierarchical pattern in Alzheimer's disease (AD) brain during disease progression, likely by trans-synaptic tau transfer between neurons. However, the tau species involved in inter-neuron propagation remains unclear. To identify tau species responsible for propagation, we examined uptake and propagation properties of different tau species derived from postmortem cortical extracts and brain interstitial fluid of tau-transgenic mice, as well as human AD cortices. Here we show that PBS-soluble phosphorylated high-molecular-weight (HMW) tau, though very low in abundance, is taken up, axonally transported, and passed on to synaptically connected neurons. Our findings suggest that a rare species of soluble phosphorylated HMW tau is the endogenous form of tau involved in propagation and could be a target for therapeutic intervention and biomarker development. Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 ethresearch Takeda Shuko joint author Wegmann Susanne joint author Cho Hansang joint author DeVos Sarah L. joint author Commins Caitlin joint author Roe Allyson D. joint author Nicholls Samantha B. joint author Carlson George A. joint author Pitstick Rose joint author Nobuhara Chloe K. joint author Costantino Isabel joint author Frosch Matthew P. joint author Müller Daniel J.; id_orcid 0000-0003-3075-0665 joint author Irimia Daniel joint author Hyman Bradley T. joint author Nature Communications London : Nature Publishing Group 6, p. 8490 2041-1723 http://hdl.handle.net/20.500.11850/105367 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/105367 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Takeda Shuko joint author ETHRESEARCH 700 1- Wegmann Susanne joint author ETHRESEARCH 700 1- Cho Hansang joint author ETHRESEARCH 700 1- DeVos Sarah L. joint author ETHRESEARCH 700 1- Commins Caitlin joint author ETHRESEARCH 700 1- Roe Allyson D. joint author ETHRESEARCH 700 1- Nicholls Samantha B. joint author ETHRESEARCH 700 1- Carlson George A. joint author ETHRESEARCH 700 1- Pitstick Rose joint author ETHRESEARCH 700 1- Nobuhara Chloe K. joint author ETHRESEARCH 700 1- Costantino Isabel joint author ETHRESEARCH 700 1- Frosch Matthew P. joint author ETHRESEARCH 700 1- Müller Daniel J.; id_orcid 0000-0003-3075-0665 joint author ETHRESEARCH 700 1- Irimia Daniel joint author ETHRESEARCH 700 1- Hyman Bradley T. joint author ETHRESEARCH 773 0- Nature Communications London : Nature Publishing Group 6, p. 8490 2041-1723 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access