Distribution patterns of tau pathology in progressive supranuclear palsy.

Coiled body Neurofibrillary tangle Progressive supranuclear palsy Propagation Richardson syndrome Sequential involvement Stage Tau Tauopathy Tufted astrocyte

Journal

Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041

Informations de publication

Date de publication:
08 2020
Historique:
received: 20 12 2019
accepted: 11 04 2020
revised: 16 03 2020
pubmed: 10 5 2020
medline: 3 8 2021
entrez: 9 5 2020
Statut: ppublish

Résumé

Progressive supranuclear palsy (PSP) is a 4R-tauopathy predominated by subcortical pathology in neurons, astrocytes, and oligodendroglia associated with various clinical phenotypes. In the present international study, we addressed the question of whether or not sequential distribution patterns can be recognized for PSP pathology. We evaluated heat maps and distribution patterns of neuronal, astroglial, and oligodendroglial tau pathologies and their combinations in different clinical subtypes of PSP in postmortem brains. We used conditional probability and logistic regression to model the sequential distribution of tau pathologies across different brain regions. Tau pathology uniformly predominates in the neurons of the pallido-nigro-luysian axis in different clinical subtypes. However, clinical subtypes are distinguished not only by total tau load but rather cell-type (neuronal versus glial) specific vulnerability patterns of brain regions suggesting distinct dynamics or circuit-specific segregation of propagation of tau pathologies. For Richardson syndrome (n = 81) we recognize six sequential steps of involvement of brain regions by the combination of cellular tau pathologies. This is translated to six stages for the practical neuropathological diagnosis by the evaluation of the subthalamic nucleus, globus pallidus, striatum, cerebellum with dentate nucleus, and frontal and occipital cortices. This system can be applied to further clinical subtypes by emphasizing whether they show caudal (cerebellum/dentate nucleus) or rostral (cortical) predominant, or both types of pattern. Defining cell-specific stages of tau pathology helps to identify preclinical or early-stage cases for the better understanding of early pathogenic events, has implications for understanding the clinical subtype-specific dynamics of disease-propagation, and informs tau-neuroimaging on distribution patterns.

Identifiants

pubmed: 32383020
doi: 10.1007/s00401-020-02158-2
pii: 10.1007/s00401-020-02158-2
pmc: PMC7360645
doi:

Substances chimiques

MAPT protein, human 0
tau Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

99-119

Subventions

Organisme : NIA NIH HHS
ID : P30 AG010124
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG017586
Pays : United States
Organisme : Medical Research Council
ID : MR/L016397/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P01 AG066597
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG062418
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS109260
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR001880
Pays : United States
Organisme : NINDS NIH HHS
ID : K23 NS088341
Pays : United States

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Auteurs

Gabor G Kovacs (GG)

Center for Neurodegenerative Disease Research (CNDR), Institute On Aging and Department of Pathology & Laboratory Medicine, University of Pennsylvania, 3600 Spruce Street, 3 Maloney Building, Philadelphia, PA, 19104-4283, USA. gabor.kovacs@uhnresearch.ca.
Tanz Centre for Research in Neurodegenerative Disease (CRND) and Department of Laboratory Medicine and Pathobiology, University of Toronto, 60 Leonard Ave, Krembil Discovery Tower, Toronto, ON, M5T 0S8, Canada. gabor.kovacs@uhnresearch.ca.
Laboratory Medicine Program and Krembil Brain Institute, University Health Network, Toronto, ON, Canada. gabor.kovacs@uhnresearch.ca.

Milica Jecmenica Lukic (MJ)

German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Clinic of Neurology, CCS, University of Belgrade, Belgrade, Republic of Serbia.

David J Irwin (DJ)

Department of Neurology, University of Pennsylvania, Philadelphia, USA.
Frontotemporal Degeneration Center, University of Pennsylvania, Philadelphia, USA.

Thomas Arzberger (T)

German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
Center for Neuropathology and Prion Research, LMU Munich, Munich, Germany.
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

Gesine Respondek (G)

German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Department of Neurology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

Edward B Lee (EB)

Center for Neurodegenerative Disease Research (CNDR), Institute On Aging and Department of Pathology & Laboratory Medicine, University of Pennsylvania, 3600 Spruce Street, 3 Maloney Building, Philadelphia, PA, 19104-4283, USA.

David Coughlin (D)

Frontotemporal Degeneration Center, University of Pennsylvania, Philadelphia, USA.
Department of Neurosciences, University of California, La Jolla, San Diego, CA, USA.

Armin Giese (A)

Center for Neuropathology and Prion Research, LMU Munich, Munich, Germany.

Murray Grossman (M)

Department of Neurology, University of Pennsylvania, Philadelphia, USA.
Frontotemporal Degeneration Center, University of Pennsylvania, Philadelphia, USA.

Carolin Kurz (C)

German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.

Corey T McMillan (CT)

Department of Neurology, University of Pennsylvania, Philadelphia, USA.
Frontotemporal Degeneration Center, University of Pennsylvania, Philadelphia, USA.

Ellen Gelpi (E)

Neurological Tissue Bank and Neurology Department, Hospital Clínic de Barcelona, Universitat de Barcelona, IDIBAPS, CERCA, Barcelona, Catalonia, Spain.
Institute of Neurology, Medical University of Vienna, Vienna, Austria.

Yaroslau Compta (Y)

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.

John C van Swieten (JC)

Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands.

Laura Donker Laat (LD)

Department Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.

Claire Troakes (C)

London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.

Safa Al-Sarraj (S)

London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.

John L Robinson (JL)

Center for Neurodegenerative Disease Research (CNDR), Institute On Aging and Department of Pathology & Laboratory Medicine, University of Pennsylvania, 3600 Spruce Street, 3 Maloney Building, Philadelphia, PA, 19104-4283, USA.

Sigrun Roeber (S)

Center for Neuropathology and Prion Research, LMU Munich, Munich, Germany.

Sharon X Xie (SX)

Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, USA.

Virginia M-Y Lee (VM)

Center for Neurodegenerative Disease Research (CNDR), Institute On Aging and Department of Pathology & Laboratory Medicine, University of Pennsylvania, 3600 Spruce Street, 3 Maloney Building, Philadelphia, PA, 19104-4283, USA.

John Q Trojanowski (JQ)

Center for Neurodegenerative Disease Research (CNDR), Institute On Aging and Department of Pathology & Laboratory Medicine, University of Pennsylvania, 3600 Spruce Street, 3 Maloney Building, Philadelphia, PA, 19104-4283, USA. trojanow@upenn.edu.

Günter U Höglinger (GU)

German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. guenter.hoeglinger@dzne.de.
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. guenter.hoeglinger@dzne.de.
Department of Neurology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. guenter.hoeglinger@dzne.de.
Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. guenter.hoeglinger@dzne.de.

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