Tau deposition patterns are associated with functional connectivity in primary tauopathies

Nicolai Franzmeier (), Matthias Brendel, Leonie Beyer, Luna Slemann, Gabor G. Kovacs, Thomas Arzberger, Carolin Kurz, Gesine Respondek, Milica J. Lukic, Davina Biel, Anna Rubinski, Lukas Frontzkowski, Selina Hummel, Andre Müller, Anika Finze, Carla Palleis, Emanuel Joseph, Endy Weidinger, Sabrina Katzdobler, Mengmeng Song, Gloria Biechele, Maike Kern, Maximilian Scheifele, Boris-Stephan Rauchmann, Robert Perneczky, Michael Rullman, Marianne Patt, Andreas Schildan, Henryk Barthel, Osama Sabri, Jost J. Rumpf, Matthias L. Schroeter, Joseph Classen, Victor Villemagne, John Seibyl, Andrew W. Stephens, Edward B. Lee, David G. Coughlin, Armin Giese, Murray Grossman, Corey T. McMillan, Ellen Gelpi, Laura Molina-Porcel, Yaroslau Compta, John C. Swieten, Laura Donker Laat, Claire Troakes, Safa Al-Sarraj, John L. Robinson, Sharon X. Xie, David J. Irwin, Sigrun Roeber, Jochen Herms, Mikael Simons, Peter Bartenstein, Virginia M. Lee, John Q. Trojanowski, Johannes Levin, Günter Höglinger and Michael Ewers
Additional contact information
Nicolai Franzmeier: University Hospital of Munich, LMU Munich
Matthias Brendel: University Hospital of Munich, LMU Munich
Leonie Beyer: University Hospital of Munich, LMU Munich
Luna Slemann: University Hospital of Munich, LMU Munich
Gabor G. Kovacs: University of Pennsylvania
Thomas Arzberger: Munich Cluster for Systems Neurology (SyNergy)
Carolin Kurz: German Center for Neurodegenerative Diseases (DZNE)
Gesine Respondek: German Center for Neurodegenerative Diseases (DZNE)
Milica J. Lukic: German Center for Neurodegenerative Diseases (DZNE)
Davina Biel: University Hospital of Munich, LMU Munich
Anna Rubinski: University Hospital of Munich, LMU Munich
Lukas Frontzkowski: University Hospital of Munich, LMU Munich
Selina Hummel: University Hospital of Munich, LMU Munich
Andre Müller: Life Molecular Imaging GmbH
Anika Finze: University Hospital of Munich, LMU Munich
Carla Palleis: Munich Cluster for Systems Neurology (SyNergy)
Emanuel Joseph: University Hospital of Munich, LMU Munich
Endy Weidinger: University Hospital of Munich, LMU Munich
Sabrina Katzdobler: University Hospital of Munich, LMU Munich
Mengmeng Song: University Hospital of Munich, LMU Munich
Gloria Biechele: University Hospital of Munich, LMU Munich
Maike Kern: University Hospital of Munich, LMU Munich
Maximilian Scheifele: University Hospital of Munich, LMU Munich
Boris-Stephan Rauchmann: University Hospital of Munich, LMU Munich
Robert Perneczky: Munich Cluster for Systems Neurology (SyNergy)
Michael Rullman: University Hospital Leipzig
Marianne Patt: University Hospital Leipzig
Andreas Schildan: University Hospital Leipzig
Henryk Barthel: University Hospital Leipzig
Osama Sabri: University Hospital Leipzig
Jost J. Rumpf: University Hospital of Munich, LMU Munich
Matthias L. Schroeter: University Hospital of Munich, LMU Munich
Joseph Classen: University Hospital Leipzig
Victor Villemagne: Department of Molecular Imaging & Therapy, Austin Health
John Seibyl: InviCRO, LLC
Andrew W. Stephens: Life Molecular Imaging GmbH
Edward B. Lee: University of Pennsylvania
David G. Coughlin: University of Pennsylvania
Armin Giese: Center for Neuropathology and Prion Research, LMU Munich
Murray Grossman: University of Pennsylvania
Corey T. McMillan: University of Pennsylvania
Ellen Gelpi: Neurological Tissue Bank and Neurology Department, Hospital Clínic de Barcelona, Universitat de Barcelona, IDIBAPS, CERCA
Laura Molina-Porcel: Neurological Tissue Bank and Neurology Department, Hospital Clínic de Barcelona, Universitat de Barcelona, IDIBAPS, CERCA
Yaroslau Compta: Parkinson’s Disease & Movement Disorders Unit, Hospital Clínic / IDIBAPS / CIBERNED (CB06/05/0018-ISCIII), / European Reference Network for Rare Neurological Diseases (ERN-RND) / Institut de Neurociències (Maria de Maeztu Center), Universitat de Barcelona
John C. Swieten: Erasmus Medical Centre
Laura Donker Laat: Erasmus Medical Center
Claire Troakes: London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Psychology and Neuroscience, Kings College London
Safa Al-Sarraj: London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Psychology and Neuroscience, Kings College London
John L. Robinson: University of Pennsylvania
Sharon X. Xie: University of Pennsylvania
David J. Irwin: Technical University of Munich
Sigrun Roeber: Center for Neuropathology and Prion Research, LMU Munich
Jochen Herms: German Center for Neurodegenerative Diseases (DZNE)
Mikael Simons: German Center for Neurodegenerative Diseases (DZNE)
Peter Bartenstein: University Hospital of Munich, LMU Munich
Virginia M. Lee: University of Pennsylvania
John Q. Trojanowski: University of Pennsylvania
Johannes Levin: Munich Cluster for Systems Neurology (SyNergy)
Günter Höglinger: German Center for Neurodegenerative Diseases (DZNE)
Michael Ewers: University Hospital of Munich, LMU Munich

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract Tau 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.

Date: 2022
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DOI: 10.1038/s41467-022-28896-3

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