TY  - JOUR
AU  - Kovacs, Gabor G.
AU  - Irwin, David J.
AU  - Jecmenica Lukic, Milica
AU  - Arzberger, Thomas
AU  - Respondek, Gesine
AU  - Lee, Edward B.
AU  - Coughlin, David
AU  - Giese, Armin
AU  - Grossman, Murray
AU  - Kurz, Carolin
AU  - McMillan, Corey T.
AU  - Gelpi, Ellen
AU  - Compta, Yaroslau
AU  - van Swieten, John C.
AU  - Laat, Laura Donker
AU  - Troakes, Claire
AU  - Al-Sarraj, Safa
AU  - Robinson, John L.
AU  - Roeber, Sigrun
AU  - Xie, Sharon X.
AU  - Lee, Virginia M.- Y.
AU  - Trojanowski, John Q.
AU  - Höglinger, Günter U.
TI  - Distribution patterns of tau pathology in progressive supranuclear palsy
JO  - Acta neuropathologica
VL  - 140
IS  - 2
SN  - 0001-6322
CY  - Heidelberg
PB  - Springer
M1  - DZNE-2020-01060
SP  - 99-119
PY  - 2020
AB  - 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.
KW  - Aged
KW  - Brain: pathology
KW  - Cohort Studies
KW  - Female
KW  - Humans
KW  - Male
KW  - Middle Aged
KW  - Supranuclear Palsy, Progressive: pathology
KW  - tau Proteins: analysis
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC7360645
C6  - pmid:32383020
DO  - DOI:10.1007/s00401-020-02158-2
UR  - https://pub.dzne.de/record/151075
ER  -