Franzmeier, Nicolai ORCID: 0000-0001-9736-2283, Brendel, Matthias ORCID: 0000-0002-9247-2843, Beyer, Leonie ORCID: 0000-0002-7358-4495, Slemann, Luna, Kovacs, Gabor G., Arzberger, Thomas, Kurz, Carolin, Respondek, Gesine, Lukic, Milica J., Biel, Davina, Rubinski, Anna, Frontzkowski, Lukas, Hummel, Selina, Muller, Andre, Finze, Anika, Palleis, Carla, Joseph, Emanuel, Weidinger, Endy, Katzdobler, Sabrina, Song, Mengmeng, Biechele, Gloria, Kern, Maike, Scheifele, Maximilian, Rauchmann, Boris-Stephan ORCID: 0000-0003-4547-6240, Perneczky, Robert, Rullman, Michael, Patt, Marianne, Schildan, Andreas ORCID: 0000-0002-9418-3826, 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 ORCID: 0000-0002-1790-7376, Al-Sarraj, Safa, Robinson, John L., Xie, Sharon X., Irwin, David J., Roeber, Sigrun, Herms, Jochen, Simons, Mikael ORCID: 0000-0001-5329-192X, Bartenstein, Peter, Lee, Virginia M., Trojanowski, John Q., Levin, Johannes ORCID: 0000-0001-5092-4306, Hoeglinger, Gunter and Ewers, Michael (2022). Tau deposition patterns are associated with functional connectivity in primary tauopathies. Nat. Commun., 13 (1). BERLIN: NATURE PORTFOLIO. ISSN 2041-1723

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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 F-18-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 drives neuronal dysfunction in 4- repeat tauopathies. Here, the authors combine tau-PET, resting-state fMRI and histopathology data, to show that brain connectivity is associated with tau deposition patterns in 4-repeat tauopathies.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Franzmeier, NicolaiUNSPECIFIEDorcid.org/0000-0001-9736-2283UNSPECIFIED
Brendel, MatthiasUNSPECIFIEDorcid.org/0000-0002-9247-2843UNSPECIFIED
Beyer, LeonieUNSPECIFIEDorcid.org/0000-0002-7358-4495UNSPECIFIED
Slemann, LunaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kovacs, Gabor G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arzberger, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurz, CarolinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Respondek, GesineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lukic, Milica J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Biel, DavinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rubinski, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frontzkowski, LukasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hummel, SelinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muller, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Finze, AnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palleis, CarlaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Joseph, EmanuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weidinger, EndyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Katzdobler, SabrinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Song, MengmengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Biechele, GloriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kern, MaikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheifele, MaximilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rauchmann, Boris-StephanUNSPECIFIEDorcid.org/0000-0003-4547-6240UNSPECIFIED
Perneczky, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rullman, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patt, MarianneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schildan, AndreasUNSPECIFIEDorcid.org/0000-0002-9418-3826UNSPECIFIED
Barthel, HenrykUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sabri, OsamaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rumpf, Jost J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeter, Matthias L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Classen, JosephUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Villemagne, VictorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seibyl, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stephens, Andrew W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Edward B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coughlin, David G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giese, ArminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grossman, MurrayUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McMillan, Corey T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gelpi, EllenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Molina-Porcel, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Compta, YaroslauUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Swieten, John C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laat, Laura DonkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Troakes, ClaireUNSPECIFIEDorcid.org/0000-0002-1790-7376UNSPECIFIED
Al-Sarraj, SafaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robinson, John L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xie, Sharon X.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Irwin, David J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roeber, SigrunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herms, JochenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simons, MikaelUNSPECIFIEDorcid.org/0000-0001-5329-192XUNSPECIFIED
Bartenstein, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Virginia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trojanowski, John Q.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Levin, JohannesUNSPECIFIEDorcid.org/0000-0001-5092-4306UNSPECIFIED
Hoeglinger, GunterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ewers, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-697349
DOI: 10.1038/s41467-022-28896-3
Journal or Publication Title: Nat. Commun.
Volume: 13
Number: 1
Date: 2022
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PROGRESSIVE SUPRANUCLEAR PALSY; ALZHEIMERS-DISEASE; PATHOLOGICAL TAU; PET; DEGENERATION; PROPAGATION; DIAGNOSIS; CRITERIA; SPREAD; MODELMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69734

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