Patterns of microglial cell activation in frontotemporal lobar degeneration
Abstract
Aims: Pathological heterogeneity within patients with frontotemporal lobar degeneration (FTLD) in general precludes the accurate assignment of diagnostic subtype in life. The aim of this study was to assess the extent of microglial cell activation in FTLD in order to determine whether it might be possible to employ this as a diagnostic marker in vivo using PET ligand [11 C](R)‐PK 11195 in order to differentiate cases of FTLD according to histological subtype. Methods: The distribution and extent of microglial cell activation was assessed semi‐quantitatively in cortical grey and subcortical white matter of CD 68 immunostained sections of frontal and temporal cortex from 78 pathologically confirmed cases of FTLD, 13 of A lzheimer's disease (AD) and 13 controls. Results: Significantly higher levels of microglial cell activation than controls occurred in all four regions in FTLD, and in three of the four regions in AD. Microglial activation was greater in frontal subcortical white matter in FTLD than AD, whereas it was higher in temporal cortical grey matter in AD than FTLD. Microglial cell activation was significantly higher in temporal subcortical white matter in FTLD‐MAPT than in other genetic (GRN, C9ORF72) or non‐genetic forms of FTLD. Conclusions: The present study suggests that high levels of microglial cell involvement in temporal lobe (subcortical white matter) might serve as a marker of inherited FTLD associated with intronic mutations in MAPT, with a relatively intense signal in this region in PET studies using [11 C](R)‐PK 11195 as microglial cell marker could indicate the presence of MAPT mutation in vivo.
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?
It is well established that an innate immune response, characterized by activated microglia, is a feature of the neuropathology of FTD.
“It is well established that an innate immune response, characterized by activated microglia, is a feature of the neuropathology of FTD (Lant et al., 2014).”
From Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum (2020) · cites this paper as Lant et al., 2014
In vivo PET and immunohistochemistry studies found increased microglial activation in the frontal and temporal cortices of patients with FTD.
“In vivo PET studies320,321 and immunohistochemistry studies322–324 have found increased microglial activation in the frontal and temporal cortices of patients with FTD.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [323]
Earlier autopsy work in FTD found increased microglial activation in tau- and TDP-43-related pathologies.
“Previous post mortem evidence in FTD reported upregulated microglial activation in both tau and TDP-related pathologies [15].”
From In vivo PET imaging of neuroinflammation in familial frontotemporal dementia (2021) · cites this paper as [15]
Cites
DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.011 · Cited by 4,936 · see citing works
A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD
Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J. C., Myllykangas, L., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.010 · Cited by 4,409 · see citing works
Self-citationAssociation of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498 · see citing works
Self-citationHyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092 · see citing works
Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17
Baker, M., Mackenzie, I. R., Pickering-Brown, S. M., Gass, J., Rademakers, R., Lindholm, C., Snowden, J., Adamson, J., Sadovnick, A. D., Rollinson, S., et al. (2006) · Nature · doi:10.1038/nature05016 · Cited by 2,058 · see citing works
Self-citationRegulation 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
Edison, P., Archer, H. A., Gerhard, A., Hinz, R., Pavese, N., Turkheimer, F. E., Hammers, A., Tai, Y. F., Fox, N., Kennedy, A., et al. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.08.001 · Cited by 513 · see citing works
Self-citationAl-Sarraj, S., King, A., Troakes, C., Smith, B., Maekawa, S., Bodi, I., Rogelj, B., Al-Chalabi, A., Hortobágyi, T., & Shaw, C. E. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0911-2 · Cited by 475 · see citing works
In vivo detection of microglial activation in frontotemporal dementia
Cagnin, A., Rossor, M., Sampson, E. L., MacKinnon, T., & Banati, R. B. (2004) · Annals of Neurology · doi:10.1002/ana.20332 · Cited by 187 · cited 1× · see citing works
“have also been successful in showing the presence of microglial activation in vivo in progressive supranuclear palsy (PSP) and cortical basal degeneration (CBD) [24,25], and also in a small cohort of FTLD patients [26].”
BackgroundA European multicentre PET study of fibrillar amyloid in Alzheimer’s disease
Nordberg, A., Carter, S. F., Rinne, J., Drzezga, A., Brooks, D. J., Vandenberghe, R., Perani, D., Forsberg, A., Långström, B., Scheinin, N., et al. (2013) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-012-2237-2 · Cited by 186 · see citing works
Gerhard, 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
Self-citationPET Imaging of Neuropathology in Tauopathies: Progressive Supranuclear Palsy
Kepe, V., Bordelon, Y., Boxer, A., Huang, S.-C., Liu, J., Thiede, F. C., Mazziotta, J. C., Mendez, M. F., Donoghue, N., Small, G. W., et al. (2013) · Journal of Alzheimer's Disease · doi:10.3233/jad-130032 · Cited by 106 · see citing works
Sensitivity and specificity of FTDC criteria for behavioral variant frontotemporal dementia
Harris, J. M., Gall, C., Thompson, J. C., Richardson, A. M. T., Neary, D., du Plessis, D., Pal, P., Mann, D. M. A., Snowden, J. S., & Jones, M. (2013) · Neurology · doi:10.1212/wnl.0b013e318292a342 · Cited by 83 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
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
Neuroinflammation in frontotemporal dementia
Bright, F., Werry, E. L., Dobson-Stone, C., Piguet, O., Ittner, L. M., Halliday, G. M., Hodges, J. R., Kiernan, M. C., Loy, C. T., Kassiou, M., et al. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0231-z · Cited by 280 · see citing works
The Role of Neuroinflammation in Dementias
Pasqualetti, G., Brooks, D. J., & Edison, P. (2015) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-015-0531-7 · Cited by 133 · see citing works
Fluid biomarkers in frontotemporal dementia: past, present and future
Swift, I. J., Sogorb-Esteve, A., Heller, C., Synofzik, M., Otto, M., Graff, C., Galimberti, D., Todd, E., Heslegrave, A. J., van der Ende, E. L., et al. (2021) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-323520 · Cited by 122 · see citing works
Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum
Bevan-Jones, W. R., Cope, T. E., Jones, P. S., Kaalund, S. S., Passamonti, L., Allinson, K., Green, O., Hong, Y. T., Fryer, T. D., Arnold, R., et al. (2020) · Brain · doi:10.1093/brain/awaa033 · Cited by 124 · see citing works
López González, I., Garcia-Esparcia, P., Llorens, F., & Ferrer, I. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17020206 · Cited by 101 · see citing works
Cerami, C., Iaccarino, L., & Perani, D. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18050993 · Cited by 75 · see citing works
Elahi, F. M., Marx, G., Cobigo, Y., Staffaroni, A. M., Kornak, J., Tosun, D., Boxer, A. L., Kramer, J. H., Miller, B. L., & Rosen, H. J. (2017) · NeuroImage: Clinical · doi:10.1016/j.nicl.2017.09.007 · Cited by 59 · see citing works
Mapping neuroinflammation in frontotemporal dementia with molecular PET imaging
Zhang, J. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0236-5 · Cited by 62 · see citing works
In vivo PET imaging of neuroinflammation in familial frontotemporal dementia
Malpetti, M., Rittman, T., Jones, P. S., Cope, T. E., Passamonti, L., Bevan-Jones, W. R., Patterson, K., Fryer, T. D., Hong, Y. T., Aigbirhio, F. I., et al. (2021) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-323698 · Cited by 43 · see citing works
Chu, M., Wen, L., Jiang, D., Liu, L., Nan, H., Yue, A., Wang, Y., Wang, Y., Qu, M., Wang, N., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02746-5 · Cited by 33 · 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
Self-citation
- Authors
- Lant, S. B., Robinson, A. C., Thompson, J. C., Rollinson, S., Pickering‐Brown, S., Snowden, J. S., Davidson, Y. S., Gerhard, A., & Mann, D. M. A.
- Affiliations
- University of Manchester (GB)
- Clinical and Cognitive Sciences Research Group Institute of Brain, Behaviour and Mental Health Faculty of Medical and Human Sciences University of Manchester, Salford Royal Hospital Salford UK
- Corresponding author
- Mann, David M. A.
- ORCID
- Venue
- Neuropathology and Applied Neurobiology
- Publisher
- Wiley
- Published
- 2014-09-25
- Volume
- 40
- Issue
- 6
- Pages
- 686-696
- ISSN
- 0305-1846 (ISSN-L)
- 1365-2990
- OpenAlex
- W1895989725
- Cited by
- 102
- References
- 13
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 18 · 2023: 13 · 2022: 9 · 2021: 7 · 2020: 13 · 2019: 7 · 2018: 9 · 2017: 9 · 2016: 1 · 2015: 5 · 2014: 1 · 2013: 1
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropathology and Applied Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- Wellcome Trust (089701)
- 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
- frontotemporal lobar degeneration, microglial activation, [11C](R)-PK11195, positron emission tomography, Alzheimer's disease, MAPT mutations, GRN mutations, C9orf72, diagnostic biomarkers
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Male, Middle Aged, Biomarkers, Microglia, Frontotemporal Lobar Degeneration, White Matter, Gray Matter
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
