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|Title:||Tau deposition patterns are associated with functional connectivity in primary tauopathies.||Austin Authors:||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||Affiliation:||Institute for Stroke and Dementia Research, University Hospital of Munich, LMU Munich, Munich, Germany..
Department of Neurology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany..
Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA..
Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA..
Department of Neurosciences, University of California, La Jolla, San Diego, CA, USA..
Frontotemporal Degeneration Center, University of Pennsylvania, Philadelphia, PA, USA..
Molecular Neuroimaging, A Division of inviCRO, New Haven, CT, USA..
InviCRO, LLC, Boston, MA, USA..
Medicine (University of Melbourne)
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA..
Molecular Imaging and Therapy
Tanz Centre for Research in Neurodegenerative Disease (CRND) and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada..
Center for Neurodegenerative Disease Research (CNDR), Institute On Aging and Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA..
Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany..
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany..
Clinic of Neurology, CCS, University of Belgrade, Belgrade, Republic of Serbia..
Institute for Stroke and Dementia Research, University Hospital of Munich, LMU Munich, Munich, Germany..
Life Molecular Imaging GmbH, Berlin, Germany..
Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College, London, UK..
Institute of Neurology, Medical University of Vienna, Vienna, Austria..
Department of Radiology, University Hospital of Munich, LMU Munich, Munich, Germany..
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig, Germany..
Department of Nuclear Medicine, University Hospital Cologne, Cologne, Germany..
Department of Neurology, University Hospital Leipzig, Leipzig, Germany..
Center for Neuropathology and Prion Research, LMU Munich, Munich, Germany..
Neurological Tissue Bank and Neurology Department, Hospital Clínic de Barcelona, Universitat de Barcelona, IDIBAPS, CERCA, Barcelona, Catalonia, Spain..
Parkinson's Disease & Movement Disorders Unit, Hospital Clínic / IDIBAPS / CIBERNED (CB06/05/0018-ISCIII), / European Reference Network for Rare Neurological Diseases (ERN-RND) / Institut de Neurociències (Maria de Maeztu Center), Universitat de Barcelona, Barcelona, Catalonia, Spain..
Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands..
Department Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands..
London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK..
Department of Neurology, University Hospital of Munich, LMU Munich, Munich, Germany..
Department of Neurology, Hannover Medical School, Hannover, Germany..
Laboratory Medicine Program and Krembil Brain Institute, University Health Network, Toronto, ON, Canada..
Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany..
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany..
Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany..
|Issue Date:||15-Mar-2022||Date:||2022||Publication information:||Nature communications 2022; 13(1): 1362||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.||URI:||https://ahro.austin.org.au/austinjspui/handle/1/29049||DOI:||10.1038/s41467-022-28896-3||ORCID:||http://orcid.org/0000-0001-9736-2283
|Journal:||Nature communications||PubMed URL:||35292638||PubMed URL:||https://pubmed.ncbi.nlm.nih.gov/35292638/||Type:||Journal Article|
|Appears in Collections:||Journal articles|
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