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Reactive microglia are positive for HLA‐DR in the substantia nigra of Parkinson's and Alzheimer's disease brains
Abstract
We detected large numbers of HLA-DR-positive reactive microglia (macrophages), along with Lewy bodies and free melanin, in the substantia nigra of all cases studied with Parkinson's disease (5) and parkinsonism with dementia (PD) (5). We found similar, but less extensive, pathology in the substantia nigra of six of nine cases of dementia of the Alzheimer type (DAT) but in only one of 11 age-matched nonneurologic cases. All dementia cases with a premortem diagnosis of DAT or PD showed large numbers of HLA-DR-positive reactive microglia and significant plaque and tangle counts in the hippocampus, as well as reduced cortical choline acetyltransferase activity. One of 11 nondemented controls showed mild evidence of similar cortical pathology. These data indicate that HLA-DR-positive reactive microglia are a sensitive index of neuropathologic activity. They suggest a frequent coexistence of DAT- and Parkinson-type pathology in elderly patients.
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In the citing paper
“Early evidence revealed the presence of reactive microglia expressing Histocompatibility Leukocyte Antigen DR-Isotype (HLA-DR) in the SNpc of human post mortem brain tissue [6].”
From Intrastriatal injection of preformed alpha-synuclein fibrils alters central and peripheral immune cell profiles in non-transgenic mice (2019) · cites this paper as [6]
In the citing paper
“Reactive microglia expressing HLA-DR are abundant in the substantia nigra of PD patients60.”
From Microglia in neurodegeneration (2018) · cites this paper as [60]
In the citing paper
“In 1988, reactive microglia were first observed in the substantia nigra (SN) of postmortem brain tissue from PD patients.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [210]
In the citing paper
“Intense microgliosis around extraneuronal neuromelanin (released by dying neurons) has been identified in the substantia nigra of patients with Parkinson’s disease.125,126”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [125]
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Items 1,001–1,040 of 1,040
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Ohgami, T., Kitamoto, T., Shin, R. W., Kaneko, Y., Ogomori, K., & Tateishi, J. (1991) · Acta Neuropathologica · doi:10.1007/bf00305864 · Cited by 64
Thomas, M., Le, W. D., & Jankovic, J. (2003) · Clinical Neuropharmacology · doi:10.1097/00002826-200301000-00005 · Cited by 62
Behavioral and transcriptomic analysis of Trem2-null mice: not all knockout mice are created equal
Kang, S. S., Kurti, A., Baker, K. E., Liu, C.-C., Colonna, M., Ulrich, J. D., Holtzman, D. M., Bu, G., & Fryer, J. D. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddx366 · Cited by 62
Liu, S.-Y., Qiao, H.-W., Song, T.-B., Liu, X.-L., Yao, Y.-X., Zhao, C.-S., Barret, O., Xu, S.-L., Cai, Y.-N., Tamagnan, G. D., et al. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02574-z · Cited by 62
Tauroursodeoxycholic acid (TUDCA) is neuroprotective in a chronic mouse model of Parkinson’s disease
Cuevas, E., Burks, S., Raymick, J., Robinson, B., Gómez-Crisóstomo, N. P., Escudero-Lourdes, C., Lopez, A. G. G., Chigurupati, S., Hanig, J., Ferguson, S. A., et al. (2022) · Nutritional Neuroscience · doi:10.1080/1028415x.2020.1859729 · Cited by 57
Neuroprotective activities of natural products from marine macroalgae during 1999–2015
Alghazwi, M., Kan, Y. Q., Zhang, W., Gai, W. P., Garson, M. J., & Smid, S. (2016) · Journal of Applied Phycology · doi:10.1007/s10811-016-0908-2 · Cited by 58
JNK and NADPH oxidase involved in fluoride-induced oxidative stress in BV-2 microglia cells
Yan, L., Liu, S., Wang, C., Wang, F., Song, Y., Yan, N., Xi, S., Liu, Z., & Sun, G. (2013) · Mediators of Inflammation · doi:10.1155/2013/895975 · Cited by 58
Quintero, E. M., Willis, L., Singleton, R., Harris, N., Huang, P., Bhat, N., & Granholm, A.-C. (2006) · Brain Research · doi:10.1016/j.brainres.2006.03.104 · Cited by 58
Interleukin-6 triggers toxic neuronal iron sequestration in response to pathological α-synuclein
Sterling, J. K., Kam, T.-I., Guttha, S., Park, H., Baumann, B., Mehrabani-Tabari, A. A., Schultz, H., Anderson, B., Alnemri, A., Chou, S.-C., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110358 · Cited by 58
Joers, V., Masilamoni, G., Kempf, D., Weiss, A. R., Rotterman, T. M., Murray, B., Yalcin-Cakmakli, G., Voll, R. J., Goodman, M. M., Howell, L., et al. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105027 · Cited by 56
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Leggio, L., Paternò, G., Vivarelli, S., Falzone, G. G., Giachino, C., Marchetti, B., & Iraci, N. (2021) · Aging and disease · doi:10.14336/ad.2021.0527 · Cited by 55
Sugama, S., Takenouchi, T., Fujita, M., Kitani, H., & Hashimoto, M. (2011) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.11.002 · Cited by 55
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Liang, Y., Zhou, T., Chen, Y., Lin, D., Jing, X., Peng, S., Zheng, D., Zeng, Z., Lei, M., Wu, X., et al. (2017) · NeuroToxicology · doi:10.1016/j.neuro.2017.09.015 · Cited by 55
Peng, J., Xie, L., Stevenson, F. F., Melov, S., Di Monte, D. A., & Andersen, J. K. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.3447-06.2006 · Cited by 53
Scheffold, A., Holtman, I. R., Dieni, S., Brouwer, N., Katz, S.-F., Jebaraj, B. M. C., Kahle, P. J., Hengerer, B., Lechel, A., Stilgenbauer, S., et al. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0364-x · Cited by 53
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Gul, A., Bakht, J., & Mehmood, F. (2019) · Journal of the Chinese Medical Association · doi:10.1016/j.jcma.2018.07.004 · Cited by 52
Wang, L., Liu, Y., Yan, S., Du, T., Fu, X., Gong, X., Zhou, X., Zhang, T., & Wang, X. (2020) · Aging and disease · doi:10.14336/ad.2019.0615 · Cited by 49
Lin, Z., Chen, C., Yang, D., Ding, J., Wang, G., & Ren, H. (2021) · Cell Death & Disease · doi:10.1038/s41419-021-04002-1 · Cited by 49
Alrouji, M., Al-Kuraishy, H. M., Al-Gareeb, A. I., Saad, H. M., & Batiha, G. E.-S. (2023) · Inflammopharmacology · doi:10.1007/s10787-023-01192-2 · Cited by 47
Li, S., Bi, G., Han, S., & Huang, R. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.744942 · Cited by 45
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Capucciati, A., Zucca, F. A., Monzani, E., Zecca, L., Casella, L., & Hofer, T. (2021) · Antioxidants · doi:10.3390/antiox10060824 · Cited by 36
Gerecke, K. M., Kolobova, A., Allen, S., & Fawer, J. L. (2013) · Brain Research · doi:10.1016/j.brainres.2013.02.027 · Cited by 37
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Zhang, W., Gao, J.-H., Yan, Z.-F., Huang, X.-Y., Guo, P., Sun, L., Liu, Z., Hu, Y., Zuo, L.-J., Yu, S.-Y., et al. (2018) · Molecular Neurobiology · doi:10.1007/s12035-016-0308-2 · Cited by 37
Walker, D. G., Lue, L.-F., Tang, T. M., Adler, C. H., Caviness, J. N., Sabbagh, M. N., Serrano, G. E., Sue, L. I., & Beach, T. G. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.03.007 · Cited by 33
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Liang, Y., Zheng, D., Peng, S., Lin, D., Jing, X., Zeng, Z., Chen, Y., Huang, K., Xie, Y., Zhou, T., et al. (2020) · Toxicology in Vitro · doi:10.1016/j.tiv.2019.104690 · Cited by 33
Ernest James Phillips, T., & Maguire, E. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.652593 · Cited by 33
Mendes, M. O., Rosa, A. I., Carvalho, A. N., Nunes, M. J., Dionísio, P., Rodrigues, E., Costa, D., Duarte-Silva, S., Maciel, P., Rodrigues, C. M. P., et al. (2019) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2019.01.003 · Cited by 31
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Bartl, M., Xylaki, M., Bähr, M., Weber, S., Trenkwalder, C., & Mollenhauer, B. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105744 · Cited by 33
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Roberts, R. F., & Fon, E. A. (2016) · Cell Research · doi:10.1038/cr.2016.104 · Cited by 30
Wang, D., Gao, H., Qin, Q., Li, J., Zhao, J., Qu, Y., Li, J., Xiong, Y., Min, Z., Mao, Z., et al. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-04881-w · Cited by 25
Drobny, A., Ngo, P. A., Neurath, M. F., Zunke, F., & López-Posadas, R. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.655123 · Cited by 24
Aspects of innate immunity and Parkinson's disease
Huang, Y., & Halliday, G. M. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00033 · Cited by 22
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Langston, J. W., Forno, L. S., Tetrud, J., Reeves, A. G., Kaplan, J. A., & Karluk, D. (1999) · Annals of Neurology · doi:10.1002/1531-8249(199910)46:4 · Cited by 1
Mattson, M. (1999) · doi:10.1002/(sici)1097-4547(19991001)58:1
Metadata
- Authors
- McGeer, P. L., Itagaki, S., Boyes, B. E., & McGeer, E. G.
- Affiliations
- University of British Columbia (CA)
- Venue
- Neurology
- Published
- 1988-08
- Volume
- 38
- Issue
- 8
- Pages
- 1285-1285
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W1974924674
- Cited by
- 2,990
- References
- 0
- Citations by year
- 2026: 98 · 2025: 130 · 2024: 148 · 2023: 148 · 2022: 175 · 2021: 159 · 2020: 159 · 2019: 129 · 2018: 131 · 2017: 93 · 2016: 108 · 2015: 111 · 2014: 120 · 2013: 116 · 2012: 127
- FWCI
- 10.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- reactive microglia, HLA-DR, substantia nigra, Parkinson's disease, Alzheimer's disease, Lewy bodies, melanin, amyloid plaques, neurofibrillary tangles, choline acetyltransferase, hippocampus
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain Chemistry, Dementia, Female, HLA-D Antigens, HLA-DR Antigens, Humans, Male, Melanins, Middle Aged, Neuroglia, Parkinson Disease, Substantia Nigra
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