Tau deposition patterns are associated with functional connectivity in primary tauopathies
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Published:2022-03-15
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Franzmeier NicolaiORCID, Brendel MatthiasORCID, Beyer LeonieORCID, Slemann Luna, Kovacs Gabor G.ORCID, Arzberger Thomas, Kurz Carolin, Respondek Gesine, Lukic Milica J., Biel Davina, Rubinski Anna, Frontzkowski Lukas, Hummel Selina, Müller Andre, Finze AnikaORCID, Palleis Carla, Joseph Emanuel, Weidinger Endy, Katzdobler SabrinaORCID, Song Mengmeng, Biechele Gloria, Kern Maike, Scheifele Maximilian, Rauchmann Boris-Stephan, Perneczky RobertORCID, Rullman Michael, Patt Marianne, Schildan AndreasORCID, Barthel Henryk, Sabri Osama, Rumpf Jost J., Schroeter Matthias L., Classen Joseph, Villemagne Victor, Seibyl John, Stephens Andrew W.ORCID, Lee Edward B., Coughlin David G.ORCID, Giese Armin, Grossman Murray, McMillan Corey T., Gelpi Ellen, Molina-Porcel LauraORCID, Compta Yaroslau, van Swieten John C., Laat Laura Donker, Troakes ClaireORCID, Al-Sarraj Safa, Robinson John L., Xie Sharon X., Irwin David J.ORCID, Roeber Sigrun, Herms JochenORCID, Simons Mikael, Bartenstein Peter, Lee Virginia M., Trojanowski John Q.ORCID, Levin Johannes, Höglinger GünterORCID, Ewers MichaelORCID
Abstract
AbstractTau pathology is the main driver of neuronal dysfunction in 4-repeat tauopathies, including cortico-basal degeneration and progressive supranuclear palsy. Tau is assumed to spread prion-like across connected neurons, but the mechanisms of tau propagation are largely elusive in 4-repeat tauopathies, characterized not only by neuronal but also by astroglial and oligodendroglial tau accumulation. Here, we assess whether connectivity is associated with 4R-tau deposition patterns by combining resting-state fMRI connectomics with both 2nd generation 18F-PI-2620 tau-PET in 46 patients with clinically diagnosed 4-repeat tauopathies and post-mortem cell-type-specific regional tau assessments from two independent progressive supranuclear palsy patient samples (n = 97 and n = 96). We find that inter-regional connectivity is associated with higher inter-regional correlation of both tau-PET and post-mortem tau levels in 4-repeat tauopathies. In regional cell-type specific post-mortem tau assessments, this association is stronger for neuronal than for astroglial or oligodendroglial tau, suggesting that connectivity is primarily associated with neuronal tau accumulation. Using tau-PET we find further that patient-level tau patterns are associated with the connectivity of subcortical tau epicenters. Together, the current study provides combined in vivo tau-PET and histopathological evidence that brain connectivity is associated with tau deposition patterns in 4-repeat tauopathies.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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