Immunological signatures in frontotemporal lobar degeneration
Open accessAbstract
Purpose of review: Over the last year, research into the immunological and inflammatory signatures of frontotemporal lobar degeneration (FTLD) has accelerated greatly. Herein, we highlight recently proposed roles of brain-resident microglia as well as peripheral myeloid cells in frontotemporal dementia (FTD)-spectrum disorders. Recent findings: Recent unbiased genetic, transcriptomic, and proteomic surveys using human data confirm significantly altered immune-function genes as well as transcript and protein modules associated with inflammatory and immune function. Beyond human studies, novel animal models indicate important roles for both microglia and monocytes, and central involvement of genes such as Trem2, Apoe, and Tbk1. Summary: The importance of neuroinflammatory activity in FTD pathophysiology is unambiguous, but whether this activity is primarily beneficial or detrimental remains unclear, with variable results reported for distinct disease paradigms. Going forward, it will be crucial to determine which types of microglial and peripheral myeloid responses are favorable, in response to which specific proteinopathies, and at which point in disease course.
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?
Brain ageing is accompanied by lysosomal dysfunction and neuroinflammation, which collectively accelerate the occurrence and development of FTLD.
“Additionally, brain ageing is accompanied by lysosomal dysfunction and neuroinflammation,198 which collectively accelerate the occurrence and development of FTLD.”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [198]
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
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493 · see citing works
<i>TREM2</i> Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020 · see citing works
Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O’Loughlin, E., Xu, Y., Fanek, Z., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.08.008 · Cited by 2,979 · see citing works
Microglia in Alzheimer’s disease
Hansen, D. V., Hanson, J. E., & Sheng, M. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201709069 · Cited by 1,935 · see citing works
TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer’s Disease Model
Wang, Y., Cella, M., Mallinson, K., Ulrich, J. D., Young, K. L., Robinette, M. L., Gilfillan, S., Krishnan, G. M., Sudhakar, S., Zinselmeyer, B. H., et al. (2015) · Cell · doi:10.1016/j.cell.2015.01.049 · Cited by 1,736 · see citing works
TREM2 Maintains Microglial Metabolic Fitness in Alzheimer’s Disease
Ulland, T. K., Song, W. M., Huang, S. C.-C., Ulrich, J. D., Sergushichev, A., Beatty, W. L., Loboda, A. A., Zhou, Y., Cairns, N. J., Kambal, A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.023 · Cited by 1,263 · see citing works
ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy
Initiative, A. D. N., Shi, Y., Yamada, K., Liddelow, S. A., Smith, S. T., Zhao, L., Luo, W., Tsai, R. M., Spina, S., Grinberg, L. T., et al. (2017) · Nature · doi:10.1038/nature24016 · Cited by 1,220 · see citing works
Lin, Y.-T., Seo, J., Gao, F., Feldman, H. M., Wen, H.-L., Penney, J., Cam, H. P., Gjoneska, E., Raja, W. K., Cheng, J., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.05.008 · Cited by 1,125 · see citing works
Yeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C., & Sheng, M. (2016) · Neuron · doi:10.1016/j.neuron.2016.06.015 · Cited by 943 · see citing works
Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia
Freischmidt, A., Wieland, T., Richter, B., Ruf, W., Schaeffer, V., Müller, K., Marroquin, N., Nordin, F., Hübers, A., Weydt, P., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4000 · Cited by 786 · see citing works
Friedman, B. A., Srinivasan, K., Ayalon, G., Meilandt, W. J., Lin, H., Huntley, M. A., Cao, Y., Lee, S.-H., Haddick, P. C. G., Ngu, H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.066 · Cited by 662 · see citing works
Vainchtein, I. D., Chin, G., Cho, F. S., Kelley, K. W., Miller, J. G., Chien, E. C., Liddelow, S. A., Nguyen, P. T., Nakao-Inoue, H., Dorman, L. C., et al. (2018) · Science · doi:10.1126/science.aal3589 · Cited by 657 · see citing works
Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)
Atagi, Y., Liu, C.-C., Painter, M. M., Chen, X.-F., Verbeeck, C., Zheng, H., Li, X., Rademakers, R., Kang, S. S., Xu, H., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.679043 · Cited by 587 · see citing works
The heritability and genetics of frontotemporal lobar degeneration
Rohrer, J. D., Guerreiro, R., Vandrovcova, J., Uphill, J., Reiman, D., Beck, J., Isaacs, A. M., Authier, A., Ferrari, R., Fox, N. C., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181bf997a · Cited by 536 · 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
TBK1 Suppresses RIPK1-Driven Apoptosis and Inflammation during Development and in Aging
Xu, D., Jin, T., Zhu, H., Chen, H., Ofengeim, D., Zou, C., Mifflin, L., Pan, L., Amin, P., Li, W., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.041 · Cited by 461 · see citing works
Gadani, S. P., Walsh, J. T., Smirnov, I., Zheng, J., & Kipnis, J. (2015) · Neuron · doi:10.1016/j.neuron.2015.01.013 · Cited by 359 · see citing works
Comparison of family histories in FTLD subtypes and related tauopathies
Goldman, J. S., Farmer, J. M., Wood, E. M., Johnson, J. K., Boxer, A. L., Neuhaus, J. M., Lomen‐Hoerth, C., Wilhelmsen, K. C., Lee, V. M. Y., Grossman, M., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000187068.92184.63 · Cited by 349 · see citing works
Pottier, C., Bieniek, K. F., Finch, N., van de Vorst, M., Baker, M., Perkersen, R., Brown, P., Ravenscroft, T., van Blitterswijk, M., Nicholson, A. M., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1436-x · Cited by 312 · see citing works
The identity and function of microglia in neurodegeneration
Song, W. M., & Colonna, M. (2018) · Nature Immunology · doi:10.1038/s41590-018-0212-1 · Cited by 308 · see citing works
Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism
Song, W. M., Joshita, S., Zhou, Y., Ulland, T. K., Gilfillan, S., & Colonna, M. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20171529 · Cited by 305 · see citing works
Genetic Control of Human Brain Transcript Expression in Alzheimer Disease
Webster, J. A., Gibbs, J. R., Clarke, J., Ray, M., Zhang, W., Holmans, P., Rohrer, K., Zhao, A., Marlowe, L., Kaleem, M., et al. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.03.011 · Cited by 304 · see citing works
The Triggering Receptor Expressed on Myeloid Cells 2 Binds Apolipoprotein E
Bailey, C. C., DeVaux, L. B., & Farzan, M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.677286 · Cited by 303 · see citing works
Spiller, K. J., Restrepo, C. R., Khan, T., Dominique, M. A., Fang, T. C., Canter, R. G., Roberts, C. J., Miller, K. R., Ransohoff, R. M., Trojanowski, J. Q., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0083-7 · Cited by 301 · see citing works
Matarin, M., Salih, D. A., Yasvoina, M., Cummings, D. M., Guelfi, S., Liu, W., Nahaboo Solim, M. A., Moens, T. G., Paublete, R. M., Ali, S. S., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2014.12.041 · Cited by 290 · see citing works
Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
Kang, S. S., Ebbert, M. T. W., Baker, K. E., Cook, C., Wang, X., Sens, J. P., Kocher, J.-P., Petrucelli, L., & Fryer, J. D. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180653 · Cited by 260 · see citing works
TREM2and Neurodegenerative Disease
Reitz, C., & Mayeux, R. P. (2013) · New England Journal of Medicine · doi:10.1056/nejmc1306509 · Cited by 254 · see citing works
Sayed, F. A., Telpoukhovskaia, M., Kodama, L., Li, Y., Zhou, Y., Le, D., Hauduc, A., Ludwig, C., Gao, F., Clelland, C., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1811411115 · Cited by 229 · see citing works
Distinct genetic forms of frontotemporal dementia
Seelaar, H., Kamphorst, W., Rosso, S. M., Azmani, A., Masdjedi, R., de Koning, I., Maat-Kievit, J. A., Anar, B., Kaat, L. D., Breedveld, G. J., et al. (2008) · Neurology · doi:10.1212/01.wnl.0000319702.37497.72 · Cited by 216 · see citing works
Greenhalgh, A. D., Zarruk, J. G., Healy, L. M., Jesudasan, S. J. B., Jhelum, P., Salmon, C. K., Formanek, A., Russo, M. V., Antel, J. P., McGavern, D. B., et al. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2005264 · Cited by 212 · see citing works
Li, G., Adesnik, H., Li, J., Long, J., Nicoll, R. A., Rubenstein, J. L. R., & Pleasure, S. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4602-07.2008 · Cited by 209 · see citing works
Broce, I., Karch, C. M. M., Wen, N., Fan, C. C., Wang, Y., Tan, C. H., Kouri, N., Ross, O. A., Höglinger, G. U., Müller, U., et al. (2018) · PLoS Medicine · doi:10.1371/journal.pmed.1002487 · Cited by 184 · see citing works
Self-citationUmoh, M. E., Dammer, E. B., Dai, J., Duong, D. M., Lah, J. J., Levey, A. I., Gearing, M., Glass, J. D., & Seyfried, N. T. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201708202 · Cited by 154 · see citing works
A rare IL33 loss-of-function mutation reduces blood eosinophil counts and protects from asthma
Smith, D. E., Helgason, H., Sulem, P., Björnsdóttir, U. S., Lim, A. C., Sveinbjörnsson, G., Hasegawa, H., Brown, M. E., Ketchem, R. R., Gavala, M. L., et al. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006659 · Cited by 140 · see citing works
Chen-Plotkin, A. S., Geser, F., Plotkin, J. B., Clark, C. M., Kwong, L. K., Yuan, W., Grossman, M., Van Deerlin, V. M., Trojanowski, J. Q., & Lee, V. M.-Y. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn023 · Cited by 135 · see citing works
Sjogren, M. (2004) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2003.019422 · Cited by 125 · see citing works
Ferrari, R., Wang, Y., Vandrovcová, J., Guelfi, S., Witeolar, A., Karch, C. M. M., Schork, A. J., Fan, C. C., Brewer, J. B., International Genomics of Alzheimer's Project (IGAP), et al. (2016) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2016-314411 · Cited by 122 · see citing works
Self-citationInternational FTD-Genomics Consortium (IFGC), Yokoyama, J. S., Karch, C. M., Fan, C. C., Bonham, L. W., Kouri, N., Ross, O. A., Rademakers, R., Kim, J., Wang, Y., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1693-y · Cited by 99 · see citing works
Self-citationCXCR4 involvement in neurodegenerative diseases
Bonham, L. W., Karch, C. M. M., Fan, C. C., Tan, C. H., Geier, E. G., Wang, Y., Wen, N., Broce, I., Li, Y., Barkovich, M. J., et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-017-0049-7 · Cited by 95 · see citing works
Self-citationLund, H., Pieber, M., Parsa, R., Grommisch, D., Ewing, E., Kular, L., Han, J., Zhu, K., Nijssen, J., Hedlund, E., et al. (2018) · Nature Immunology · doi:10.1038/s41590-018-0091-5 · Cited by 86 · see citing works
Carlock, C., Wu, J., Shim, J., Moreno‐González, I., Pitcher, M. R., Hicks, J., Suzuki, A., Iwata, J., Quevado, J., & Lou, Y. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.142 · Cited by 59 · see citing works
Sjögren, M. J. C., & Wallin, A. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00303-7 · Cited by 30 · see citing works
Su, W., Shi, Z., Liu, S., Wang, X., Liu, S., & Ji, Y. (2018) · Annals of Human Genetics · doi:10.1111/ahg.12241 · Cited by 16 · see citing works
Protein network analysis reveals selectively vulnerable regions and biological processes in FTD
Bonham, L. W., Steele, N. Z. R., Karch, C. M. M., Manzoni, C., Geier, E. G., Wen, N., Ofori-Kuragu, A., Momeni, P., Hardy, J., Miller, Z., et al. (2018) · Neurology Genetics · doi:10.1212/nxg.0000000000000266 · Cited by 16 · see citing works
Self-citationRelevance of raised cerebrospinal fluid monocyte levels in patients with frontotemporal dementia
Pawlowski, M., Lueg, G., Groß, C. C., Johnen, A., Krämer, J., Weckesser, M., Wiendl, H., Meuth, S. G., & Duning, T. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.09.032 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165 · see citing works
A predictive coding framework of allostatic–interoceptive overload in frontotemporal dementia
Migeot, J. A., Duran-Aniotz, C. A., Signorelli, C. M., Piguet, O., & Ibáñez, A. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.08.005 · Cited by 76 · see citing works
Allostatic interoception and brain health: From neurodegeneration to social adversities
Migeot, J., & Ibáñez, A. (2025) · Encyclopedia of the Human Brain · doi:10.1016/b978-0-12-820480-1.00025-5 · Cited by 10 · see citing works
- Authors
- Sirkis, D. W., Bonham, L. W., Karch, C. M., & Yokoyama, J. S.
- Affiliations
- University of California, San Francisco (US)
- Washington University in St. Louis (US)
- Corresponding author
- Yokoyama, Jennifer S.
- Venue
- Current Opinion in Neurology
- Published
- 2019-04
- Volume
- 32
- Issue
- 2
- Pages
- 272-278
- ISSN
- 1350-7540 (ISSN-L)
- 1473-6551
- PMC
- PMC8025661
- OpenAlex
- W2913294727
- Cited by
- 14
- References
- 45
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 1
- FWCI
- 0.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Aging (K01AG049152)
- 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, frontotemporal dementia, neuroinflammation, microglia, monocytes, TREM2, apolipoprotein E, TBK1, proteinopathies, immune function genes, animal models
- MeSH terms
- Animals, Disease Models, Animal, Humans, Inflammation, Mice, Frontotemporal Lobar Degeneration
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
