Amyloid Beta and Tau Cooperate to Cause Reversible Behavioral and Transcriptional Deficits in a Model of Alzheimer's Disease.

Autor:	Pickett EK; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK., Herrmann AG; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK., McQueen J; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK; UK Dementia Research Institute at Edinburgh, George Square, Edinburgh EH8 9JZ, UK., Abt K; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK., Dando O; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK; UK Dementia Research Institute at Edinburgh, George Square, Edinburgh EH8 9JZ, UK., Tulloch J; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK; UK Dementia Research Institute at Edinburgh, George Square, Edinburgh EH8 9JZ, UK., Jain P; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK., Dunnett S; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK., Sohrabi S; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK., Fjeldstad MP; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK., Calkin W; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK., Murison L; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK., Jackson RJ; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK; MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA., Tzioras M; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK; UK Dementia Research Institute at Edinburgh, George Square, Edinburgh EH8 9JZ, UK., Stevenson A; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK; UK Dementia Research Institute at Edinburgh, George Square, Edinburgh EH8 9JZ, UK., d'Orange M; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK., Hooley M; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK; UK Dementia Research Institute at Edinburgh, George Square, Edinburgh EH8 9JZ, UK., Davies C; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK; UK Dementia Research Institute at Edinburgh, George Square, Edinburgh EH8 9JZ, UK., Colom-Cadena M; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK; UK Dementia Research Institute at Edinburgh, George Square, Edinburgh EH8 9JZ, UK., Anton-Fernandez A; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK; UK Dementia Research Institute at Edinburgh, George Square, Edinburgh EH8 9JZ, UK., King D; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK; UK Dementia Research Institute at Edinburgh, George Square, Edinburgh EH8 9JZ, UK., Oren I; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK., Rose J; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK; UK Dementia Research Institute at Edinburgh, George Square, Edinburgh EH8 9JZ, UK., McKenzie CA; Centre for Clinical Brain Sciences and Sudden Death Brain Bank, University of Edinburgh, Edinburgh EH16 4SB, UK., Allison E; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK., Smith C; Centre for Clinical Brain Sciences and Sudden Death Brain Bank, University of Edinburgh, Edinburgh EH16 4SB, UK., Hardt O; McGill University Department of Psychology, Montreal QC H3A 1B1, Canada; The University of Edinburgh Simons Initiative for the Developing Brain, George Square, Edinburgh EH8 9JZ, UK., Henstridge CM; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK., Hardingham GE; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK; UK Dementia Research Institute at Edinburgh, George Square, Edinburgh EH8 9JZ, UK., Spires-Jones TL; The University of Edinburgh Centre for Discovery Brain Sciences, 1 George Square, Edinburgh EH8 9JZ, UK; UK Dementia Research Institute at Edinburgh, George Square, Edinburgh EH8 9JZ, UK. Electronic address: tara.spires-jones@ed.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2019 Dec 10; Vol. 29 (11), pp. 3592-3604.e5.
DOI:	10.1016/j.celrep.2019.11.044
Abstrakt:	A key knowledge gap blocking development of effective therapeutics for Alzheimer's disease (AD) is the lack of understanding of how amyloid beta (Aβ) peptide and pathological forms of the tau protein cooperate in causing disease phenotypes. Within a mouse tau-deficient background, we probed the molecular, cellular, and behavioral disruption triggered by the influence of wild-type human tau on human Aβ-induced pathology. We find that Aβ and tau work cooperatively to cause a hyperactivity behavioral phenotype and to cause downregulation of transcription of genes involved in synaptic function. In both our mouse model and human postmortem tissue, we observe accumulation of pathological tau in synapses, supporting the potential importance of synaptic tau. Importantly, tau reduction in the mice initiated after behavioral deficits emerge corrects behavioral deficits, reduces synaptic tau levels, and substantially reverses transcriptional perturbations, suggesting that lowering synaptic tau levels may be beneficial in AD. (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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