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

Nat Commun. 2022 Mar 15;13(1):1362. doi: 10.1038/s41467-022-28896-3. PMID: 35292638; PMCID: PMC8924216

Authors/Editors: Franzmeier N, Brendel M, Beyer L, Slemann L, Kovacs GG, Arzberger T, Kurz C, Respondek G, Lukic MJ, Biel D, Rubinski A, Frontzkowski L, Hummel S, Müller A, Finze A, Palleis C, Joseph E, Weidinger E, Katzdobler S, Song M, Biechele G, Kern M, Scheifele M, Rauchmann BS, Perneczky R, Rullman M, Patt M, Schildan A, Barthel H, Sabri O, Rumpf JJ, Schroeter ML, Classen J, Villemagne V, Seibyl J, Stephens AW, Lee EB, Coughlin DG, Giese A, Grossman M, McMillan CT, Gelpi E, Molina-Porcel L, Compta Y, van Swieten JC, Laat LD, Troakes C, Al-Sarraj S, Robinson JL, Xie SX, Irwin DJ, Roeber S, Herms J, Simons M, Bartenstein P, Lee VM, Trojanowski JQ, Levin J, Höglinger G, Ewers M.
Publication Date: 2022

04_franzmeier

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 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.

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