Journal Article

DZNE-2020-01060

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Distribution patterns of tau pathology in progressive supranuclear palsy

Kovacs, G. G. ; Irwin, D. J. ; Jecmenica Lukic, M.DZNE* ; Arzberger, T.DZNE* ; Respondek, G.DZNE* ; Lee, E. B. ; Coughlin, D. ; Giese, A. ; Grossman, M. ; Kurz, C.DZNE* ; McMillan, C. T. ; Gelpi, E. ; Compta, Y. ; van Swieten, J. C. ; Laat, L. D. ; Troakes, C. ; Al-Sarraj, S. ; Robinson, J. L. ; Roeber, S. ; Xie, S. X. ; Lee, V. M. -Y. ; Trojanowski, J. Q. ; Höglinger, G. U. (Last author)DZNE*

2020
Springer Heidelberg

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Please use a persistent id in citations: doi:10.1007/s00401-020-02158-2

Abstract: 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.

Keyword(s): Aged (MeSH) ; Brain: pathology (MeSH) ; Cohort Studies (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Supranuclear Palsy, Progressive: pathology (MeSH) ; tau Proteins: analysis (MeSH)

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Contributing Institute(s):

1. München common (München common)
2. Translational Neurodegeneration (AG Höglinger 1)
3. Clinical Neurodegeneration (AG Levin)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2020

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; SCOPUS ; Web of Science Core Collection

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