Endogenous pathology in tauopathy mice progresses via brain networks.

Autor:	Ramirez DMO; Department of Neurology, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center; Dallas, TX, USA., Whitesell JD; Allen Institute for Brain Science; Seattle, WA, USA.; Cajal Neuroscience; Seattle, WA, USA., Bhagwat N; Allen Institute for Brain Science; Seattle, WA, USA.; McConnell Brain Imaging Centre, The Neuro (Montreal Neurological Institute-Hospital), McGill University; Montreal, Quebec, Canada., Thomas TL; Center for Alzheimer's and Neurodegenerative Diseases, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center; Dallas, TX, USA., Ajay AD; Department of Neurology, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center; Dallas, TX, USA., Nawaby A; Department of Neurology, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center; Dallas, TX, USA., Delatour B; Paris Brain Institute (ICM), CNRS UMR 7225, INSERM U1127, Sorbonne Université, Hôpital de la Pitié-Salpêtrière; Paris, France., Bay S; Unité de Chimie des Biomolécules, Institut Pasteur, Université Paris Cité, CNRS UMR 3523; Paris, France., LaFaye P; Antibody Engineering Platform, Institut Pasteur, Université Paris Cité, CNRS UMR 3528; Paris, France., Knox JE; Allen Institute for Brain Science; Seattle, WA, USA., Harris JA; Allen Institute for Brain Science; Seattle, WA, USA., Meeks JP; Department of Neuroscience, University of Rochester Medical School; Rochester, NY, USA., Diamond MI; Center for Alzheimer's and Neurodegenerative Diseases, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center; Dallas, TX, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 May 24. Date of Electronic Publication: 2023 May 24.
DOI:	10.1101/2023.05.23.541792
Abstrakt:	Neurodegenerative tauopathies are hypothesized to propagate via brain networks. This is uncertain because we have lacked precise network resolution of pathology. We therefore developed whole-brain staining methods with anti-p-tau nanobodies and imaged in 3D PS19 tauopathy mice, which have pan-neuronal expression of full-length human tau containing the P301S mutation. We analyzed patterns of p-tau deposition across established brain networks at multiple ages, testing the relationship between structural connectivity and patterns of progressive pathology. We identified core regions with early tau deposition, and used network propagation modeling to determine the link between tau pathology and connectivity strength. We discovered a bias towards retrograde network-based propagation of tau. This novel approach establishes a fundamental role for brain networks in tau propagation, with implications for human disease. Competing Interests: Competing interests: Authors declare that they have no competing interests.
Databáze:	MEDLINE
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