Tau deposition patterns are associated with functional connectivity in primary tauopathies.

2022-03-15

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 L

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

Journal Article

http://orcid.org/0000-0001-9736-2283

http://orcid.org/0000-0002-9247-2843

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http://orcid.org/0000-0002-9418-3826

http://orcid.org/0000-0001-5052-6586

http://orcid.org/0000-0003-4111-0102

http://orcid.org/0000-0003-4068-8578

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http://orcid.org/0000-0001-7587-6187

http://orcid.org/0000-0001-5231-1714

0000-0002-5832-9875

10.1038/s41467-022-28896-3

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.

link

Nature communications 2022; 13(1): 1362

Nature communications