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; Ewers, Michael     «

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,...     »

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.      «

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...     »