Regional distribution of cortical microglia parallels that of neurofibrillary tangles in Alzheimer's disease
Abstract
It has been postulated that microglia contribute to the development of neurofibrillary tangles (NFT) in Alzheimer's disease (AD). We compared the distribution of microglia with that of NFT in both AD and non-AD cases. In AD cases, we found that the extent of area covered by Ricinus communic agglutinin-1 labeled microglia generally paralleled NFT frequency and distribution. Microglia occupied the greatest area in tangle-rich periallocortex/allocortex, a lesser area in association cortex, and the smallest area in tangle-poor primary cortex. Interestingly, this pattern was also present in non-AD cases where there were few to no NFT. These findings suggest that regional variations in microglial distribution may constitute, at least in part, a template for the development of NFT.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Two papers used Ricinus communis agglutinin-1 immunohistochemistry to compare microglia counts; both reported significantly more RCA-1-labelled microglia in Alzheimer's disease in the inferomedial temporal lobe and the association cortex, periallocortex/allocortex and primary cortex.
“Both reported significantly more RCA-1-labelled microglia in AD in the inferomedial temporal lobe115 and the association cortex, periallocortex/allocortex and primary cortex, respectively.116”
From Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review (2018) · cites this paper as [116]
Microglial density is proportional to neurofibrillary tangle frequency and distribution.
“This finding is further supported by evidence from AD cases demonstrating that microglial density is proportional to neurofibrillary tangle frequency and distribution (94).”
From The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease (2019) · cites this paper as [94]
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
Diagnosis of Alzheimer's Disease
Khachaturian, Z. S. (1985) · Archives of Neurology · doi:10.1001/archneur.1985.04060100083029 · Cited by 2,499 · see citing works
Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain
Lawson, L. J., Perry, V. H., Dri, P., & Gordon, S. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90229-w · Cited by 2,045 · see citing works
Profound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer’s Disease
Gómez-Isla, T., Price, J. L., McKeel Jr., D. W., Morris, J. C., Growdon, J. H., & Hyman, B. T. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-14-04491.1996 · Cited by 1,796 · see citing works
Arnold, S. E., Hyman, B. T., Flory, J., Damasio, A. R., & Van Hoesen, G. W. (1991) · Cerebral Cortex · doi:10.1093/cercor/1.1.103 · Cited by 1,380 · see citing works
Banati, R. B., Gehrmann, J., Schubert, P., & Kreutzberg, G. W. (1993) · Glia · doi:10.1002/glia.440070117 · Cited by 1,020 · see citing works
MICROGLIA AS MEDIATORS OF INFLAMMATORY AND DEGENERATIVE DISEASES
González-Scarano, F., & Baltuch, G. (1999) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.22.1.219 · Cited by 984 · see citing works
Interleukin-1 Expression in Different Plaque Types in Alzheimerʼs Disease
Griffin, W. S. T., Sheng, J. G., Roberts, G. W., & Mrak, R. E. (1995) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199503000-00014 · Cited by 546 · see citing works
Any way you cut it: A new journal policy for the use of unbiased counting methods
Saper, C. B. (1996) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19960101)364:1 · Cited by 226 · see citing works
Glial-Neuronal Interactions in Alzheimer Disease
Sheng, J. G., Mrak, R. E., & Griffin, W. S. T. (1997) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199703000-00007 · Cited by 215 · see citing works
BOBINSKI, M., WEGIEL, J., TARNAWSKI, M., BOBINSKI, M., REISBERG, B., DE LEON, M. J., MILLER, D. C., & WISNIEWSKI, H. M. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199704000-00010 · Cited by 208 · see citing works
Chapter 32 Hippocampal formation: anatomy and the patterns of pathology in Alzheimer's disease
Hoesen, G. W. V., & Hyman, B. T. (1990) · Progress in brain research · doi:10.1016/s0079-6123(08)61268-6 · Cited by 201 · see citing works
Sheng, J. G., Mrak, R. E., & Griffin, W. S. T. (1995) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1995.tb01063.x · Cited by 181 · see citing works
Das, S., & Potter, H. (1995) · Neuron · doi:10.1016/0896-6273(95)90300-3 · Cited by 166 · see citing works
DIPATRE, P. L., & GELMAN, B. B. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199702000-00004 · Cited by 157 · see citing works
Gehrmann, J., Banati, R. B., & Kreutzberg, G. W. (1993) · Journal of Neuroimmunology · doi:10.1016/0165-5728(93)90191-z · Cited by 133 · 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
Hutchins, K. D., Dickson, D. W., Rashbaum, W. K., & Lyman, W. D. (1990) · Developmental Brain Research · doi:10.1016/0165-3806(90)90109-c · Cited by 92 · see citing works
Microglia are associated with the extracellular neurofibrillary tangles of alzheimer disease
Cras, P. P., Kawai, M., Siedlak, S. L., & Perry, G. L. (1991) · Brain Research · doi:10.1016/0006-8993(91)90783-r · Cited by 84 · see citing works
McKenzie, J. C., Berman, N. E. J., Thomas, C. R., et al. (1994) · Glia · doi:10.1002/glia.440120308 · Cited by 41 · see citing works
Self-citationSeverity of Dementia in Alzheimer Disease and Neurofibrillary Tangles in Multiple Brain Regions
Samuel, W., Henderson, V. W., & Miller, C. A. (1991) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199100510-00001 · Cited by 31 · see citing works
Kobayashi, K., Muramori, F., Aoki, T., Hayashi, M., Miyazu, K., Fukutani, Y., Mukai, M., & Koshino, F. (1997) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017015 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Hopperton, K. E., Mohammad, D., Trépanier, M. O., Giuliano, V, & Bazinet, R. P. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.246 · Cited by 567 · see citing works
Leyns, C. E. G., Ulrich, J. D., Finn, M. B., Stewart, F. R., Koscal, L. J., Remolina Serrano, J., Robinson, G. O., Anderson, E., Colonna, M., & Holtzman, D. M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1710311114 · Cited by 517 · see citing works
“Microgliosis, or activation of the innate immune cells in the brain, is an additional pathological signature routinely found in regions affected by abundant plaques and tangles (2, 3).”
BackgroundMicroglial activation and tau propagate jointly across Braak stages
Pascoal, T. A., Benedet, A. L., Ashton, N. J., Kang, M. S., Therriault, J., Chamoun, M., Savard, M., Lussier, F. Z., Tissot, C., Karikari, T. K., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01456-w · Cited by 490 · see citing works
Microglia Phenotypes in Aging and Neurodegenerative Diseases
Wendimu, M. Y., & Hooks, S. B. (2022) · Cells · doi:10.3390/cells11132091 · Cited by 336 · see citing works
Genes and pathways underlying regional and cell type changes in Alzheimer’s disease
Miller, J. A., Woltjer, R. L., Goodenbour, J. M., Horvath, S., & Geschwind, D. H. (2013) · Genome Medicine · doi:10.1186/gm452 · Cited by 275 · see citing works
Luo, W., Liu, W., Hu, X., Hanna, M., Caravaca, A., & Paul, S. M. (2015) · Scientific Reports · doi:10.1038/srep11161 · Cited by 241 · 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
The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease
Kokiko-Cochran, O. N., & Godbout, J. P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00672 · Cited by 128 · see citing works
Microglia display modest phagocytic capacity for extracellular tau oligomers
Majerova, P., Zilkova, M., Kazmerova, Z., Kovac, A., Paholikova, K., Kovacech, B., Zilka, N., & Novak, M. (2014) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0161-z · Cited by 90 · see citing works
The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease
Bonham, L. W., Sirkis, D. W., & Yokoyama, J. S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01170 · Cited by 83 · see citing works
Misfolded Truncated Protein τ Induces Innate Immune Response via MAPK Pathway
Kovac, A., Zilka, N., Kazmerova, Z., Cente, M., Zilkova, M., & Novak, M. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100216 · Cited by 75 · see citing works
Patterns of Microglial Cell Activation in Alzheimer Disease and Frontotemporal Lobar Degeneration
Taipa, R., Brochado, P., Robinson, A., Reis, I., Costa, P., Mann, D. M., Melo Pires, M., & Sousa, N. (2017) · Neurodegenerative Diseases · doi:10.1159/000457127 · Cited by 37 · see citing works
- Authors
- Sheffield, L. G., Marquis, J. G., & Berman, N. E. J.
- Affiliations
- SUNY Downstate Health Sciences University (US)
- University of Kansas (US)
- University of Kansas Medical Center (US)
- Corresponding author
- Berman, Nancy E.J
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2000-05
- Volume
- 285
- Issue
- 3
- Pages
- 165-168
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2051566636
- Cited by
- 96
- References
- 22
- Citations by year
- 2025: 5 · 2024: 10 · 2023: 8 · 2022: 6 · 2021: 13 · 2020: 4 · 2019: 8 · 2018: 6 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 4 · 2012: 5
- FWCI
- 0.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p30ag010182-05)
- National Institute on Aging (P30AG10182)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-02528)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- microglia, neurofibrillary tangles, Alzheimer's disease, regional distribution, allocortex, association cortex, primary cortex, neuroinflammation
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cerebral Cortex, Female, Humans, Male, Neurofibrillary Tangles, Microglia
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
