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000151075 1001_ $$00000-0003-3841-5511$$aKovacs, Gabor G.$$b0
000151075 245__ $$aDistribution patterns of tau pathology in progressive supranuclear palsy
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000151075 520__ $$aProgressive supranuclear palsy (PSP) is a 4R-tauopathy predominated by subcortical pathology in neurons, astrocytes, and oligodendroglia associated with various clinical phenotypes. In the present international study, we addressed the question of whether or not sequential distribution patterns can be recognized for PSP pathology. We evaluated heat maps and distribution patterns of neuronal, astroglial, and oligodendroglial tau pathologies and their combinations in different clinical subtypes of PSP in postmortem brains. We used conditional probability and logistic regression to model the sequential distribution of tau pathologies across different brain regions. Tau pathology uniformly predominates in the neurons of the pallido-nigro-luysian axis in different clinical subtypes. However, clinical subtypes are distinguished not only by total tau load but rather cell-type (neuronal versus glial) specific vulnerability patterns of brain regions suggesting distinct dynamics or circuit-specific segregation of propagation of tau pathologies. For Richardson syndrome (n = 81) we recognize six sequential steps of involvement of brain regions by the combination of cellular tau pathologies. This is translated to six stages for the practical neuropathological diagnosis by the evaluation of the subthalamic nucleus, globus pallidus, striatum, cerebellum with dentate nucleus, and frontal and occipital cortices. This system can be applied to further clinical subtypes by emphasizing whether they show caudal (cerebellum/dentate nucleus) or rostral (cortical) predominant, or both types of pattern. Defining cell-specific stages of tau pathology helps to identify preclinical or early-stage cases for the better understanding of early pathogenic events, has implications for understanding the clinical subtype-specific dynamics of disease-propagation, and informs tau-neuroimaging on distribution patterns.
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000151075 542__ $$2Crossref$$i2020-05-07$$uhttps://creativecommons.org/licenses/by/4.0
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000151075 650_2 $$2MeSH$$aAged
000151075 650_2 $$2MeSH$$aBrain: pathology
000151075 650_2 $$2MeSH$$aCohort Studies
000151075 650_2 $$2MeSH$$aFemale
000151075 650_2 $$2MeSH$$aHumans
000151075 650_2 $$2MeSH$$aMale
000151075 650_2 $$2MeSH$$aMiddle Aged
000151075 650_2 $$2MeSH$$aSupranuclear Palsy, Progressive: pathology
000151075 650_2 $$2MeSH$$atau Proteins: analysis
000151075 7001_ $$aIrwin, David J.$$b1
000151075 7001_ $$0P:(DE-2719)2812616$$aJecmenica Lukic, Milica$$b2$$udzne
000151075 7001_ $$0P:(DE-2719)2811333$$aArzberger, Thomas$$b3
000151075 7001_ $$0P:(DE-2719)2811600$$aRespondek, Gesine$$b4
000151075 7001_ $$aLee, Edward B.$$b5
000151075 7001_ $$00000-0003-4111-0102$$aCoughlin, David$$b6
000151075 7001_ $$0P:(DE-HGF)0$$aGiese, Armin$$b7
000151075 7001_ $$aGrossman, Murray$$b8
000151075 7001_ $$0P:(DE-2719)9000176$$aKurz, Carolin$$b9
000151075 7001_ $$aMcMillan, Corey T.$$b10
000151075 7001_ $$aGelpi, Ellen$$b11
000151075 7001_ $$aCompta, Yaroslau$$b12
000151075 7001_ $$avan Swieten, John C.$$b13
000151075 7001_ $$aLaat, Laura Donker$$b14
000151075 7001_ $$aTroakes, Claire$$b15
000151075 7001_ $$aAl-Sarraj, Safa$$b16
000151075 7001_ $$aRobinson, John L.$$b17
000151075 7001_ $$aRoeber, Sigrun$$b18
000151075 7001_ $$aXie, Sharon X.$$b19
000151075 7001_ $$aLee, Virginia M.- Y.$$b20
000151075 7001_ $$0P:(DE-HGF)0$$aTrojanowski, John Q.$$b21
000151075 7001_ $$0P:(DE-2719)2811373$$aHöglinger, Günter U.$$b22$$eLast author
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000151075 773__ $$0PERI:(DE-600)1458410-4$$a10.1007/s00401-020-02158-2$$gVol. 140, no. 2, p. 99 - 119$$n2$$p99-119$$tActa neuropathologica$$v140$$x0001-6322$$y2020
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