TY  - JOUR
AU  - Franzmeier, Nicolai
AU  - Brendel, Matthias
AU  - Beyer, Leonie
AU  - Slemann, Luna
AU  - Kovacs, Gabor G
AU  - Arzberger, Thomas
AU  - Kurz, Carolin
AU  - Respondek, Gesine
AU  - Jecmenica Lukic, Milica
AU  - Biel, Davina
AU  - Rubinski, Anna
AU  - Frontzkowski, Lukas
AU  - Hummel, Selina
AU  - Müller, Andre
AU  - Finze, Anika
AU  - Palleis, Carla
AU  - Joseph, Emanuel
AU  - Weidinger, Endy
AU  - Katzdobler, Sabrina
AU  - Song, Mengmeng
AU  - Biechele, Gloria
AU  - Kern, Maike
AU  - Scheifele, Heinrich Maximilian
AU  - Rauchmann, Boris Stephan
AU  - Perneczky, Robert
AU  - Rullman, Michael
AU  - Patt, Marianne
AU  - Schildan, Andreas
AU  - Barthel, Henryk
AU  - Sabri, Osama
AU  - Rumpf, Jost J
AU  - Schroeter, Matthias L
AU  - Classen, Joseph
AU  - Villemagne, Victor
AU  - Seibyl, John
AU  - Stephens, Andrew W
AU  - Lee, Edward B
AU  - Coughlin, David G
AU  - Giese, Armin
AU  - Grossman, Murray
AU  - McMillan, Corey T
AU  - Gelpi, Ellen
AU  - Molina-Porcel, Laura
AU  - Compta, Yaroslau
AU  - van Swieten, John C
AU  - Laat, Laura Donker
AU  - Troakes, Claire
AU  - Al-Sarraj, Safa
AU  - Robinson, John L
AU  - Xie, Sharon X
AU  - Irwin, David J
AU  - Roeber, Sigrun
AU  - Herms, Jochen
AU  - Simons, Mikael
AU  - Bartenstein, Peter
AU  - Lee, Virginia M
AU  - Trojanowski, John Q
AU  - Levin, Johannes
AU  - Höglinger, Günter
AU  - Ewers, Michael
TI  - Tau deposition patterns are associated with functional connectivity in primary tauopathies.
JO  - Nature Communications
VL  - 13
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2022-00446
SP  - 1362
PY  - 2022
AB  - 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.
KW  - Brain: metabolism
KW  - Humans
KW  - Magnetic Resonance Imaging
KW  - Supranuclear Palsy, Progressive: diagnostic imaging
KW  - Supranuclear Palsy, Progressive: pathology
KW  - Tauopathies: diagnostic imaging
KW  - Tauopathies: pathology
KW  - tau Proteins: metabolism
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:35292638
C2  - pmc:PMC8924216
DO  - DOI:10.1038/s41467-022-28896-3
UR  - https://pub.dzne.de/record/163707
ER  -