Tau deposition patterns are associated with functional connectivity in primary tauopathies

Franzmeier, Nicolai; Brendel, Matthias; Beyer, Leonie; Slemann, Luna; Kovacs, Gabor G.; Arzberger, Thomas; Kurz, Carolin; Respondek, Gesine; Lukic, Milica J.; Biel, Davina; Rubinski, Anna; Frontzkowski, Lukas; Hummel, Selina; Müller, Andre; Finze, Anika; Palleis, Carla; Joseph, Emanuel; Weidinger, Endy; Katzdobler, Sabrina; Song, Mengmeng; Biechele, Gloria; Kern, Maike; Scheifele, Maximilian; Rauchmann, Boris-Stephan; Perneczky, Robert; Rullman, Michael; Patt, Marianne; Schildan, Andreas; Barthel, Henryk; Sabri, Osama; Rumpf, Jost J.; Schroeter, Matthias L.; Classen, Joseph; Villemagne, Victor; Seibyl, John; Stephens, Andrew W.; Lee, Edward B.; Coughlin, David G.; Giese, Armin; Grossman, Murray; McMillan, Corey T.; Gelpi, Ellen; Molina-Porcel, Laura; Compta, Yaroslau; van Swieten, John C.; Laat, Laura Donker; Troakes, Claire; Al-Sarraj, Safa; Robinson, John L.; Xie, Sharon X.; Irwin, David J.; Roeber, Sigrun; Herms, Jochen; Simons, Mikael; Bartenstein, Peter; Lee, Virginia M.; Trojanowski, John Q.; Levin, Johannes; Höglinger, Günter and Ewers, Michael (15. March 2022): Tau deposition patterns are associated with functional connectivity in primary tauopathies. In: Nature Communications, Vol. 13

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 2 nd generation 18 F-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.

• Item Type: Journal article
• Form of publication: Publisher's Version
• Faculties: Medicine > Medical Center of the University of Munich > Clinic and Polyclinic for Nuclear Medicine; Medicine > Munich Cluster for Systems Neurology (SyNergy)
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 2041-1723
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198