Distribution patterns of tau pathology in progressive supranuclear palsy
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Progressive supranuclear palsy arises from the aggregation of tau protein in neuroglial cells, most prominently in the basal ganglia, diencephalon, and brainstem.
“Progressive supranuclear palsy (PSP) is a devastating neurodegenerative disorder caused by the neuro-glial aggregation of tau protein, particularly in the basal ganglia, diencephalon, and brainstem1,2.”
From Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy (2020) · cites this paper as [2]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Measurement of Observer Agreement for Categorical Data
Landis, J. R., & Koch, G. G. (1977) · Biometrics · doi:10.2307/2529310 · Cited by 81,148 · see citing works
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Staging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777 · see citing works
Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria
Höglinger, G. U., Respondek, G., Stamelou, M., Kurz, C., Josephs, K. A., Lang, A. E., Mollenhauer, B., Müller, U., Nilsson, C., Whitwell, J. L., et al. (2017) · Movement Disorders · doi:10.1002/mds.26987 · Cited by 2,374 · see citing works
Self-citationHauw, J., Daniel, S. E., Dickson, D. W., Horoupian, D. S., Jellinger, K. A., Lantos, P. L., McKee, A. C., Tabaton, M., & Litvan, I. (1994) · Neurology · doi:10.1212/wnl.44.11.2015 · Cited by 854 · see citing works
Williams, D. R., de Silva, R., Paviour, D. C., Pittman, A. M., Watt, H., Kilford, L., Holton, J. L., Révész, T., & Lees, A. J. (2005) · Brain · doi:10.1093/brain/awh488 · Cited by 733 · see citing works
Robinson, J. L., Lee, E. B., Xie, S. X., Rennert, L., Suh, E., Bredenberg, C., Caswell, C., Van Deerlin, V. M., Yan, N., Yousef, A., et al. (2018) · Brain · doi:10.1093/brain/awy146 · Cited by 729 · see citing works
Self-citationInvited review: Neuropathology of tauopathies: principles and practice
Kovacs, G. G. (2015) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12208 · Cited by 492 · see citing works
Self-citationStaging of Argyrophilic Grains: An Age-Associated Tauopathy
Saito, Y., Ruberu, N. N., Sawabe, M., Arai, T., Tanaka, N., Kakuta, Y., Yamanouchi, H., & Murayama, S. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.9.911 · Cited by 432 · see citing works
Neuropathologic differentiation of progressive supranuclear palsy and corticobasal degeneration
Dickson, D. W. (1999) · Journal of Neurology · doi:10.1007/bf03161076 · Cited by 424 · see citing works
Williams, D. R., Holton, J. L., Strand, C., Pittman, A. M., de Silva, R., Lees, A. J., & Révész, T. (2007) · Brain · doi:10.1093/brain/awm104 · Cited by 415 · see citing works
Neuropathology of variants of progressive supranuclear palsy
Dickson, D. W., Ahmed, Z., Algom, A. A., Tsuboi, Y., & Josephs, K. A. (2010) · Current Opinion in Neurology · doi:10.1097/wco.0b013e32833be924 · Cited by 386 · see citing works
Respondek, G., Stamelou, M., Kurz, C., Ferguson, L. W., Rajput, A. H., Chiu, W. Z., Swieten, J. C. V., Troakes, C., Sarraj, S. A., Gelpí, E., et al. (2014) · Movement Disorders · doi:10.1002/mds.26054 · Cited by 384 · see citing works
Self-citationKovács, G. G., Milenković, I., Wöehrer, A., Höftberger, R., Gelpí, E., Haberler, C., Hönigschnabl, S., Reiner‐Concin, A., Heinzl, H., Jungwirth, S., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1157-y · Cited by 360 · see citing works
A walk through tau therapeutic strategies
Jadhav, S., Ávila, J., Schöll, M., Kovács, G. G., Kövari, E., Škrabana, R., Evans, L., Kontseková, E., Malawska, B., de Silva, R., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0664-z · Cited by 286 · see citing works
Mechanisms of Cell-to-Cell Transmission of Pathological Tau: A Review
Gibbons, G. S., Lee, V. M. Y., & Trojanowski, J. Q. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2018.2505 · Cited by 257 · see citing works
Self-citationMolecular pathology of neurodegenerative diseases: principles and practice
Kovács, G. G. (2019) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2019-205952 · Cited by 243 · see citing works
Toledo, J. B., Van Deerlin, V. M., Lee, E. B., Suh, E., Baek, Y., Robinson, J. L., Xie, S. X., McBride, J., Wood, E. M., Schuck, T., et al. (2014) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2013.06.003 · Cited by 234 · see citing works
Self-citationRösler, T. W., Marvian, A. T., Brendel, M., Nykänen, N.-P., Höllerhage, M., Schwarz, S. C., Hopfner, F., Koeglsperger, T., Respondek, G., Schweyer, K., et al. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101644 · Cited by 219 · see citing works
Self-citationDeep clinical and neuropathological phenotyping of P ick disease
Irwin, D. J., Brettschneider, J., McMillan, C. T., Cooper, F. I., Olm, C. A., Arnold, S. E., Deerlin, V. M. V., Seeley, W. W., Miller, B. L., Lee, E. B., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24559 · Cited by 204 · see citing works
Self-citationEarly diagnosis of dementia: neuropsychology
Pasquier, F. (1999) · Journal of Neurology · doi:10.1007/s004150050299 · Cited by 192 · see citing works
Schonhaut, D. R., McMillan, C. T., Spina, S., Dickerson, B. C., Siderowf, A., Devous, M. D., Tsai, R., Winer, J., Russell, D. S., Litvan, I., et al. (2017) · Annals of Neurology · doi:10.1002/ana.25060 · Cited by 175 · see citing works
Self-citationAstrogliopathy predominates the earliest stage of corticobasal degeneration pathology
Ling, H., Kovács, G. G., Vonsattel, J. P., Davey, K., Mok, K. Y., Hardy, J., Morris, H. R., Warner, T. T., Holton, J. L., & Révész, T. (2016) · Brain · doi:10.1093/brain/aww256 · Cited by 134 · see citing works
Kovács, G. G., Xie, S. X., Robinson, J. L., Lee, E. B., Smith, D. H., Schuck, T., Lee, V. M. ‐., & Trojanowski, J. Q. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0552-y · Cited by 133 · see citing works
Self-citationKovacs, G. G., Robinson, J. L., Xie, S. X., Lee, E. B., Grossman, M., Wolk, D. A., Irwin, D. J., Weintraub, D., Kim, C. F., Schuck, T., et al. (2017) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlx007 · Cited by 132 · see citing works
Self-citationfor the EANM-EAN Task Force for the recommendation of FDG PET for Dementing Neurodegenerative Disorders, Walker, Z., Gandolfo, F., et al. (2018) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-018-4031-2 · Cited by 132 · see citing works
Tsuboi, Y., Josephs, K. A., Boeve, B. F., Litvan, I., Caselli, R. J., Caviness, J. N., Uitti, R. J., Bott, A. D., & Dickson, D. W. (2005) · Movement Disorders · doi:10.1002/mds.20478 · Cited by 129 · see citing works
Halliday, G. M., Macdonald, V., & Henderson, J. M. (2005) · Brain · doi:10.1093/brain/awh596 · Cited by 115 · see citing works
Intrinsic connectivity network disruption in progressive supranuclear palsy
Gardner, R. C., Boxer, A. L., Trujillo, A. J., Mirsky, J. B., Guo, C. C., Gennatas, E. D., Heuer, H. W., Fine, E. M., Zhou, J. H., Kramer, J. H., et al. (2013) · Annals of Neurology · doi:10.1002/ana.23844 · Cited by 106 · see citing works
Ahmed, Z., Josephs, K. A., Gonzalez, J., DelleDonne, A., & Dickson, D. W. (2007) · Brain · doi:10.1093/brain/awm301 · Cited by 103 · see citing works
Ling, H., de Silva, R., Massey, L., Courtney, R., Hondhamuni, G., Bajaj, N., Lowe, J., Holton, J., Lees, A. J., & Révész, T. (2014) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12037 · Cited by 96 · see citing works
Protein astrogliopathies in human neurodegenerative diseases and aging
Kovács, G. G., Lee, V. M., & Trojanowski, J. Q. (2017) · Brain Pathology · doi:10.1111/bpa.12536 · Cited by 89 · see citing works
Self-citationThe neuropathology of progressive supranuclear palsy
Lantos, P. L. (1994) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-6641-3_11 · Cited by 84 · see citing works
Clinicopathological Outcomes of Prospectively Followed Normal Elderly Brain Bank Volunteers
Dugger, B. N., Hentz, J. G., Adler, C. H., Sabbagh, M. N., Shill, H. A., Jacobson, S. A., Caviness, J. N., Belden, C. M., Driver‐Dunckley, E. D., Davis, K. J., et al. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000046 · Cited by 80 · see citing works
Yoshida, K., Hata, Y., Kinoshita, K., Takashima, S., Tanaka, K., & Nishida, N. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1665-7 · Cited by 78 · see citing works
Validation of the Movement Disorder Society Criteria for the Diagnosis of 4‐Repeat Tauopathies
Respondek, G., Grimm, M., Piot, I., Arzberger, T., Compta, Y., Englund, E. M., Ferguson, L. W., Gelpí, E., Roeber, S., Giese, A., et al. (2019) · Movement Disorders · doi:10.1002/mds.27872 · Cited by 73 · see citing works
Self-citationCellular and regional vulnerability in frontotemporal tauopathies
Forrest, S. L., Kril, J. J., & Halliday, G. M. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02035-7 · Cited by 71 · see citing works
Cognitive impairment in progressive supranuclear palsy is associated with tau burden
Koga, S., Parks, A. C., Kasanuki, K., Sánchez-Contreras, M., Baker, M., Josephs, K. A., Ahlskog, J. E., Uitti, R. J., Graff‐Radford, N. R., van Gerpen, J. A., et al. (2017) · Movement Disorders · doi:10.1002/mds.27198 · Cited by 65 · see citing works
Tau neuropathology correlates with FDG-PET, but not AV-1451-PET, in progressive supranuclear palsy.
Smith, R., Schöll, M., Honer, M., Nilsson, C. F., Englund, E., & Hansson, O. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1650-1 · Cited by 62 · see citing works
Allen, M., Wang, X., Serie, D., Strickland, S. L., Burgess, J. D., Koga, S., Younkin, C. S., Nguyen, T., Malphrus, K. G., Lincoln, S., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1900-5 · Cited by 58 · see citing works
Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG)
Kovács, G. G., Xie, S. X., Lee, E. B., Robinson, J. L., Caswell, C., Irwin, D. J., Toledo, J. B., Johnson, V. E., Smith, D. H., Alafuzoff, I. I., et al. (2017) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlx041 · Cited by 54 · see citing works
Self-citationNeuropathological findings of PSP in the elderly without clinical PSP: Possible incidental PSP?
Evidente, V. G. H., Adler, C. H., Sabbagh, M. N., Connor, D. J., Hentz, J. G., Caviness, J. N., Sue, L. I., & Beach, T. G. (2011) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2011.02.017 · Cited by 52 · see citing works
Patterns of Hippocampal Tau Pathology Differentiate Neurodegenerative Dementias
Milenković, I., Petrov, T., & Kovács, G. G. (2014) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000365548 · Cited by 36 · see citing works
Nogami, A., Yamazaki, M., Saito, Y., Hatsuta, H., Sakiyama, Y., Takao, M., Kimura, K., & Murayama, S. (2015) · Journal of Nippon Medical School · doi:10.1272/jnms.82.266 · Cited by 33 · see citing works
Yokoyama, Y., Toyoshima, Y., Shiga, A., Tada, M., Kitamura, H., Hasegawa, K., Onodera, O., Ikeuchi, T., Someya, T., Nishizawa, M., et al. (2015) · Brain Pathology · doi:10.1111/bpa.12265 · Cited by 32 · see citing works
Progression of two Progressive Supranuclear Palsy phenotypes with comparable initial disability
Shoeibi, A., Litvan, I., TOLOSA, E. S., del Ser, T., & Lee, E. (2019) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2019.07.010 · Cited by 31 · see citing works
Self-citationNeuropathologic basis of frontotemporal dementia in progressive supranuclear palsy
Sakae, N., Josephs, K. A., Litvan, I., Murray, M. E., Duara, R., Uitti, R. J., Wszołek, Z. K., Graff‐Radford, N. R., & Dickson, D. W. (2019) · Movement Disorders · doi:10.1002/mds.27816 · Cited by 23 · see citing works
Sakai, K., & Yamada, M. (2010) · Neuropathology · doi:10.1111/j.1440-1789.2010.01134.x · Cited by 22 · see citing works
The relationship between clinical and pathological variables in Richardson’s syndrome
Schofield, E. C., Hodges, J. R., Bak, T. H., Xuereb, J. H., & Halliday, G. M. (2011) · Journal of Neurology · doi:10.1007/s00415-011-6205-8 · Cited by 22 · see citing works
Historical Perspectives and Memories of Progressive Supranuclear Palsy
Steele, J. C. (2014) · Seminars in Neurology · doi:10.1055/s-0034-1381740 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [37]Sakae N Josephs KA Litvan I Murray ME Duara R Uitti RJ Neuropathologic basis of frontotemporal dementia in progressive supranuclear palsy Mov Disord 2019 10.1002/mds.27816 31433871 PMC6899964 · DOI
Cited by
Sorted by citations
Tauopathies: new perspectives and challenges
Zhang, Y., Wu, K.-M., Yang, L., Dong, Q., & Yu, J.-T. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00533-z · Cited by 323 · see citing works
Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy
Malpetti, M., Passamonti, L., Rittman, T., Jones, P. S., Vázquez Rodríguez, P., Bevan‐Jones, W. R., Hong, Y. T., Fryer, T. D., Aigbirhio, F. I., O'Brien, J. T., et al. (2020) · Annals of Neurology · doi:10.1002/ana.25911 · Cited by 83 · see citing works
Microglia: Friend and foe in tauopathy
Odfalk, K. F., Bieniek, K. F., & Hopp, S. C. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102306 · Cited by 60 · see citing works
In Vivo Assessment of Neuroinflammation in <scp>4‐Repeat</scp> Tauopathies
Palleis, C., Sauerbeck, J., Beyer, L., Harris, S., Schmitt, J., Morenas‐Rodriguez, E., Finze, A., Nitschmann, A., Ruch‐Rubinstein, F., Eckenweber, F., et al. (2021) · Movement Disorders · doi:10.1002/mds.28395 · Cited by 62 · see citing works
Self-citationJohnson, N. R., Yuan, P., Castillo, E., Lopez, T. P., Yue, W., Bond, A., Rivera, B. M., Sullivan, M. C., Hirouchi, M., Giles, K., et al. (2023) · Nature Communications · doi:10.1038/s41467-022-35753-w · Cited by 46 · see citing works
Strobel, J., Müller, H.-P., Ludolph, A. C., Beer, A. J., Sollmann, N., & Kassubek, J. (2023) · Cells · doi:10.3390/cells12242776 · Cited by 10 · see citing works
- Authors
- Kovacs, G. G., Lukic, M. J., Irwin, D. J., Arzberger, T., Respondek, G., Lee, E. B., Coughlin, D., Giese, A., Grossman, M., Kurz, C., 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.
- Affiliations
- University of Pennsylvania (US)
- German Center for Neurodegenerative Diseases (DE)
- University of California San Diego (US)
- Institut für Neuropathologie (DE)
- Instituto de Salud Carlos III (ES)
- King's College London (GB)
- Corresponding author
- Trojanowski, John Q.
- Höglinger, Günter U.
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2020-05-07
- Volume
- 140
- Issue
- 2
- Pages
- 99-119
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC7360645
- OpenAlex
- W3022376055
- Cited by
- 483
- References
- 50
- Citations by year
- 2026: 91 · 2025: 97 · 2024: 97 · 2023: 67 · 2022: 58 · 2021: 60 · 2020: 11
- FWCI
- 21.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Acta Neuropathologica (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DZNE Pub (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (acceptedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion, cc-by)
- mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
- Funders
- National Institutes of Health (P30 AG010124, U19 AG062418, NS088341)
- Penn Institute on Aging (Penn Institute on Aging)
- Fundació la Marató de TV3 (20141610)
- Rossy Foundation (Rossy PSP program)
- Edmond J. Safra Philanthropic Foundation (Safra Fund)
- Karl Golser Prize (Golser Prize)
- Deutsche Forschungsgemeinschaft (EXC 2145 SyNergy—ID 390857198, HO2402/18-1)
- Bundesministerium für Bildung und Forschung (01KU1403A EpiPD, 01EK1605A HitTau)
- NOMIS Stiftung (FTLD)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- progressive supranuclear palsy, tau pathology, Richardson syndrome, clinical subtypes, subthalamic nucleus, globus pallidus, striatum, cerebellum, dentate nucleus, cortical involvement, disease propagation, neuropathological staging
- MeSH terms
- Aged, Brain, Female, Humans, Male, Middle Aged, Supranuclear Palsy, Progressive, Cohort Studies, tau Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
