Microglial Activation parallels System Degeneration in progressive Supranuclear palsy and Corticobasal Degeneration
Abstract
The role of microglia in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) is unknown. To address this issue we examined 10 cases of PSP, 5 cases of CBD, and 4 normal controls. Microglial and tau burdens were determined with image analysis on brain sections that had been immunostained with monoclonal antibodies to HLA-DR and phospho-tau. We found that microglial activation was greater in PSP and CBD than normal controls, and that the microglial burden correlated with the tau burden in most areas. There were distinct patterns of microglial activation and tau pathology in PSP and CBD, with PSP showing more pathology in infratentorial structures and CBD showing more pathology in supratentorial structures. These results support the notion that PSP and CBD are distinct clinicopathologic entities. Microglial activation was not well correlated with tau pathology in the brainstem of PSP, which suggests that brainstem pathology in PSP is not exclusively due to tau pathology. While the results do not necessarily support a direct causal link between microglial activation and neurodegeneration in PSP or CBD, they nevertheless suggest that microglia play a role in disease pathogenesis.
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Several studies identified increased microglia number and activation in the substantia nigra pars compacta, subthalamic nucleus, pyramidal, extrapyramidal motor system, and cerebellar output of brain tissues from PSP patients by immunochemical postmortem analysis.
“Several studies have identified increased microglia number and activation in the substantia nigra pars compacta (SNpc),372 subthalamic nucleus,373 pyramidal, extrapyramidal motor system, and cerebellar output374 of brain tissues from PSP patients by immunochemical postmortem analysis.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [374]
In most of these regions, microglial activation was positively correlated with tau burden.
“And in most of these regions, microglial activation was positively correlated with tau burden.374”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [374]
Microglial activation, indicating neuroinflammation, is present in PSP.
“However, neuroinflammation also occurs in PSP, with microglial activation5,6, with a proposed toxic alliance between tau-mediated neurodegeneration and neuroinflammation.”
From Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy (2020) · cites this paper as [5]
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991) · Annals of Neurology · doi:10.1002/ana.410300410 · Cited by 4,397 · see citing works
Microglia: a sensor for pathological events in the CNS
Kreutzberg, G. W. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10049-7 · Cited by 4,396 · see citing works
McGeer, P. L., Itagaki, S., Boyes, B. E., & McGeer, E. G. (1988) · Neurology · doi:10.1212/wnl.38.8.1285 · Cited by 2,990 · see citing works
Litvan, I., Agid, Y., Calne, D., Campbell, G., Dubois, B., Duvoisin, R. C., Goetz, C. G., Golbe, L. I., Grafman, J., Growdon, J. H., et al. (1996) · Neurology · doi:10.1212/wnl.47.1.1 · Cited by 2,538 · see citing works
Progressive Supranuclear Palsy
Steele, J. C. (1964) · Archives of Neurology · doi:10.1001/archneur.1964.00460160003001 · Cited by 1,930 · see citing works
The `subcortical dementia' of progressive supranuclear palsy
Albert, M. L., Feldman, R. G., & Willis, A. L. (1974) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.37.2.121 · Cited by 871 · see citing works
Hauw, 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
Self-citationRogers, J., Luber-Narod, J., Styren, S. D., & Civin, W. H. (1988) · Neurobiology of Aging · doi:10.1016/s0197-4580(88)80079-4 · Cited by 743 · see citing works
Corticodentatonigral Degeneration With Neuronal Achromasia
Rebeiz, J. J., Kolodny, E. H., & Richardson, E. P. (1968) · Archives of Neurology · doi:10.1001/archneur.1968.00470310034003 · Cited by 627 · 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
Self-citationLue, L. F., Brachova, L., CIVIN, W. H., & Rogers, J. (1996) · PubMed · Cited by 299 · see citing works
Neurofibrillary Degeneration in Progressive Supranuclear Palsy and Corticobasal Degeneration
Sergeant, N., Wattez, A., & Delacourte, A. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0721243.x · Cited by 287 · see citing works
Neurodegenerative disorders with extensive tau pathology: A comparative study and review
Feany, M. Β., & Dickson, D. W. (1996) · Annals of Neurology · doi:10.1002/ana.410400204 · Cited by 279 · see citing works
Self-citationWidespread cytoskeletal pathology characterizes corticobasal degeneration.
Feany, M. Β., & Dickson, D. W. (1995) · PubMed · Cited by 276 · see citing works
Self-citationSpecific Domains of β-Amyloid from Alzheimer Plaque Elicit Neuron Killing in Human Microglia
Giulian, D., Haverkamp, L. J., Yu, J., Karshin, W. L., Tom, D., Li, J., Kirkpatrick, J. B., Kuo, Y., & Roher, A. E. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-19-06021.1996 · Cited by 266 · see citing works
Feany, M. Β., Mattiace, L. A., & Dickson, D. W. (1996) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199601000-00006 · Cited by 264 · see citing works
Self-citationTHE ROLE OF ANTI-INFLAMMATORY DRUGS IN THE PREVENTION AND TREATMENT OF ALZHEIMER'S DISEASE
Breitner, J. C. S. (1996) · Annual Review of Medicine · doi:10.1146/annurev.med.47.1.401 · Cited by 263 · see citing works
Lue, L.-F., Brachova, L., Civin, H. W., & Rogers, J. (1996) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199655100-00008 · Cited by 246 · cited 2× · see citing works
“Synaptic loss, which is considered to be a major structural basis for dementia (31), was shown to correlate better with microglial activation than to traditional histopathologic markers of AD such as senile plaques (30).”
BackgroundProgressive supranuclear palsy: neuropathologically based diagnostic clinical criteria.
Collins, S. J., Ahlskog, J. E., Parisi, J. E., & Maraganore, D. M. (1995) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.58.2.167 · Cited by 204 · see citing works
Soliveri, P., Monza, D., Paridi, D., Radice, D., Grisoli, M., Testa, D., Savoiardo, M., & Girotti, F. (1999) · Neurology · doi:10.1212/wnl.53.3.502 · Cited by 185 · see citing works
Frontal Lobe Function in Progressive Supranuclear Palsy
Grafman, J. H., Litvan, I., Gomez, C., & Chase, T. N. (1990) · Archives of Neurology · doi:10.1001/archneur.1990.00530050077015 · Cited by 162 · see citing works
Slowing of Cognitive Processing in Progressive Supranuclear Palsy
Dubois, B. (1988) · Archives of Neurology · doi:10.1001/archneur.1988.00520350032011 · Cited by 155 · see citing works
Pollock, N., Mirra, S. S., Binder, L. I., Hansen, L., & Wood, J. (1986) · The Lancet · doi:10.1016/s0140-6736(86)92212-9 · Cited by 147 · see citing works
Iwatsubo, T., Hasegawa, M., & Ihara, Y. (1994) · Acta Neuropathologica · doi:10.1007/bf00294505 · Cited by 108 · see citing works
Unusual clinical presentations of cortical‐basal ganglionic degeneration
Bergeron, C., Pollanen, M. S., Weyer, L., Black, S. E., & Lang, A. E. (1996) · Annals of Neurology · doi:10.1002/ana.410400611 · Cited by 108 · see citing works
Morphometric Analysis of Microglia in Alzheimerʼs Disease
CARPENTER, A. F., CARPENTER, P. W., & MARKESBERY, W. R. (1993) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199311000-00007 · Cited by 94 · see citing works
Psychological Dysfunction Accompanying Subcortical Dementias
Cummings, J. L., & Benson, D. F. (1988) · Annual Review of Medicine · doi:10.1146/annurev.me.39.020188.000413 · Cited by 91 · see citing works
Ikeda, K., Akiyama, H., Iritani, S., Kase, K., Arai, T., Niizato, K., Kuroki, N., & Kosaka, K. (1996) · Acta Neuropathologica · doi:10.1007/s004010050558 · Cited by 76 · see citing works
A Qualitative and Quantitative Study of Grumose Degeneration in Progressive Supranuclear Palsy
Ishizawa, K., Lin, W.-L., Tiseo, P. J., Honer, W. G., Davies, P. J., & Dickson, D. W. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.6.513 · Cited by 52 · see citing works
Self-citationPopović, M., Caballero‐Bleda, M., Puelles, L., & Popović, N. (1998) · International Journal of Neuroscience · doi:10.3109/00207459809003341 · Cited by 49 · see citing works
Lassmann, H., & Wf, H. (1993) · PubMed · Cited by 43 · see citing works
Progressive supranuclear palsy case report with pathological findings
Anzil, A. P. (1969) · Acta Neuropathologica · doi:10.1007/bf00687704 · Cited by 42 · see citing works
Computed tomographic findings in progressive supranuclear palsy: Correlation with clinical grade
Schonfeld, S. M., Golbe, L. I., Sage, J. I., et al. (1987) · Movement Disorders · doi:10.1002/mds.870020404 · Cited by 41 · see citing works
Komori, T., Shibata, N., Kobayashi, M., Sasaki, S., & Iwata, M. (1998) · Acta Neuropathologica · doi:10.1007/s004010050808 · Cited by 39 · see citing works
Gibb, W., Luthert, P., & Marsden, C. (1989) · Brain : a journal of neurology · doi:10.1093/brain/112.5.1171 · Cited by 39 · see citing works
Li, Y.-B., Kaur, C., & Ling, E. (1998) · Neuroscience Research · doi:10.1016/s0168-0102(98)00077-7 · Cited by 29 · see citing works
“Grumose degeneration” of the dentate nucleus
Arai, N. (1989) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(89)90096-8 · Cited by 28 · see citing works
MR VS CT in progressive supranuclear palsy
Masucci, E. F., Borts, F. T., Perl, S., et al. (1995) · Computerized Medical Imaging and Graphics · doi:10.1016/0895-6111(95)00014-3 · Cited by 14 · see citing works
Immunohistochemical study of a case with progressive supranuclear palsy without ophthalmoplegia
Kida, E., Barcikowska, M., & Niemczewska, M. (1992) · Acta Neuropathologica · doi:10.1007/bf00296797 · Cited by 14 · see citing works
Klegeris (1997) · doi:10.1002/(sici)1097-4547(19970715)49:2
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Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616 · see citing works
Regulation of Tau Pathology by the Microglial Fractalkine Receptor
Bhaskar, K., Konerth, M., Kokiko-Cochran, O. N., Cardona, A., Ransohoff, R. M., & Lamb, B. T. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.023 · Cited by 639 · see citing works
Maphis, N., Xu, G., Kokiko-Cochran, O. N., Jiang, S., Cardona, A., Ransohoff, R. M., Lamb, B. T., & Bhaskar, K. (2015) · Brain · doi:10.1093/brain/awv081 · Cited by 595 · see citing works
Stancu, I.-C., Cremers, N., Vanrusselt, H., Couturier, J., Vanoosthuyse, A., Kessels, S., Lodder, C., Brône, B., Huaux, F., Octave, J.-N., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-018-01957-y · Cited by 447 · see citing works
Croisier, E., Moran, L. B., Dexter, D. T., Pearce, R. K., & Graeber, M. B. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-14 · Cited by 414 · see citing works
Does corticobasal degeneration exist? A clinicopathological re-evaluation
Ling, H., O'Sullivan, S. S., Holton, J. L., Revesz, T., Massey, L. A., Williams, D. R., Paviour, D. C., & Lees, A. J. (2010) · Brain · doi:10.1093/brain/awq123 · Cited by 394 · see citing works
Tau and neuroinflammation: what impact for Alzheimer's disease and tauopathies?
Laurent, C., Buée, L., & Blum, D. (2018) · Biomedical Journal · doi:10.1016/j.bj.2018.01.003 · Cited by 348 · see citing works
Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy
Wang, C., Fan, L., Khawaja, R. R., Liu, B., Zhan, L., Kodama, L., Chin, M., Li, Y., Le, D., Zhou, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29552-6 · Cited by 333 · see citing works
Progressive Supranuclear Palsy: Pathology and Genetics
Dickson, D. W., Rademakers, R., & Hutton, M. L. (2007) · Brain Pathology · doi:10.1111/j.1750-3639.2007.00054.x · Cited by 314 · see citing works
Self-citationDirect Evidence of Internalization of Tau by Microglia In Vitro and In Vivo
Bolós, M., Llorens-Martín, M., Jurado-Arjona, J., Hernández, F., Rábano, A., & Avila, J. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-150704 · Cited by 234 · see citing works
Intersection of pathological tau and microglia at the synapse
Vogels, T., Murgoci, A.-N., & Hromádka, T. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0754-y · Cited by 197 · see citing works
Dupont, A.-C., Largeau, B., Santiago Ribeiro, M., Guilloteau, D., Tronel, C., & Arlicot, N. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040785 · Cited by 182 · see citing works
Efficacy and safety of immunization with phosphorylated tau against neurofibrillary tangles in mice
Boimel, M., Grigoriadis, N., Lourbopoulos, A., Haber, E., Abramsky, O., & Rosenmann, H. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.05.010 · Cited by 174 · see citing works
Microglial Activation Parallels System Degeneration in Multiple System Atrophy
Ishizawa, K., Komori, T., Sasaki, S., Arai, N., Mizutani, T., & Hirose, T. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.1.43 · Cited by 172 · see citing works
Self-citationGerhard, A., Trender‐Gerhard, I., Turkheimer, F., Quinn, N. P., Bhatia, K. P., & Brooks, D. J. (2006) · Movement Disorders · doi:10.1002/mds.20668 · Cited by 171 · see citing works
Desai Bradaric, B., Patel, A., Schneider, J. A., Carvey, P. M., & Hendey, B. (2012) · Journal of Neural Transmission · doi:10.1007/s00702-011-0684-8 · Cited by 139 · see citing works
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Kokiko-Cochran, O. N., & Godbout, J. P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00672 · Cited by 128 · see citing works
Is synaptic loss a unique hallmark of Alzheimer’s disease?
Scheff, S. W., Neltner, J. H., & Nelson, P. T. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.12.028 · Cited by 118 · see citing works
Imaging of microglia in patients with neurodegenerative disorders
Politis, M. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00096 · Cited by 111 · see citing works
Conway, O. J., Carrasquillo, M. M., Wang, X., Bredenberg, J. M., Reddy, J. S., Strickland, S. L., Younkin, C. S., Burgess, J. D., Allen, M., Lincoln, S. J., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0289-x · Cited by 112 · see citing works
Self-citationCytokine expression and microglial activation in progressive supranuclear palsy
Fernández-Botrán, R., Ahmed, Z., Crespo, F. A., Gatenbee, C., Gonzalez, J., Dickson, D. W., & Litvan, I. (2011) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2011.06.007 · Cited by 93 · see citing works
Self-citationJiang, S., Maphis, N. M., Binder, J., Chisholm, D., Weston, L., Duran, W., Peterson, C., Zimmerman, A., Mandell, M. A., Jett, S. D., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109720 · Cited by 92 · see citing works
Loss of tau rescues inflammation-mediated neurodegeneration
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Microglia display modest phagocytic capacity for extracellular tau oligomers
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Cook, C., Kang, S. S., Carlomagno, Y., Lin, W.-L., Yue, M., Kurti, A., Shinohara, M., Jansen-West, K., Perkerson, E., Castanedes-Casey, M., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv336 · Cited by 82 · see citing works
Self-citationNeuroinflammation 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
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Giannopoulos, P. F., Chu, J., Sperow, M., Li, J.-G., Yu, W. H., Kirby, L. G., Abood, M., & Praticò, D. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.01.015 · Cited by 48 · see citing works
RetractedJohnson, 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
Finze, A., Biechele, G., Rauchmann, B.-S., Franzmeier, N., Palleis, C., Katzdobler, S., Weidinger, E., Guersel, S., Schuster, S., Harris, S., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02188-8 · Cited by 40 · see citing works
- Authors
- Ishizawa, K., & Dickson, D. W.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Ishizawa, Keisuke
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-06
- Volume
- 60
- Issue
- 6
- Pages
- 647-657
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W2409698408
- Cited by
- 209
- References
- 41
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 13 · 2023: 9 · 2022: 7 · 2021: 15 · 2020: 19 · 2019: 12 · 2018: 17 · 2017: 6 · 2016: 13 · 2015: 8 · 2014: 9 · 2013: 6 · 2012: 6
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Foundation for Medical Education and Research (AG17216, AG03949)
- National Institutes of Health (AG03949, AG17216)
- National Institute on Aging (AG03949, P01AG003949, AG 17216, AG1449, P01AG017216)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- microglial activation, progressive supranuclear palsy, corticobasal degeneration, tau pathology, HLA-DR, phosphorylated tau, neurodegeneration, brainstem pathology, pathogenesis, clinicopathological correlation
- MeSH terms
- Aged, Aged, 80 and over, Basal Ganglia Diseases, Cerebral Cortex, Female, Humans, Immunohistochemistry, Male, Nerve Degeneration, Supranuclear Palsy, Progressive, tau Proteins, Microglia
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