The DOI matches its Crossref record; 129 of the 129 references it cites were found in a registry or an index.
TREM2 ectodomain and its soluble form in Alzheimer’s disease
Open accessAbstract
Triggering receptor expressed on myeloid cells 2 (TREM2) is a receptor mainly expressed on the surface of microglia. It mediates multiple pathophysiological processes in various diseases. Recently, TREM2 has been found to play a role in the development of Alzheimer's disease (AD). TREM2 is a transmembrane protein that is specifically expressed on microglia in the brain. It contains a long ectodomain that directly interacts with the extracellular environment to regulate microglial function. The ectodomain of TREM2 is processed by a disintegrin and metalloprotease, resulting in the release of a soluble form of TREM2 (sTREM2). Recent studies have demonstrated that sTREM2 is a bioactive molecule capable of binding ligands, activating microglia, and regulating immune responses during the AD continuum. Clinical studies revealed that sTREM2 level is elevated in cerebrospinal fluid (CSF) of AD patients, and the sTREM2 level is positively correlated with the levels of classical CSF biomarkers, namely t-tau and p-tau, indicating that it is a reliable predictor of the early stages of AD. Herein, we summarize the key results on the generation, structure, and function of sTREM2 to provide new insights into TREM2-related mechanisms underlying AD pathogenesis and to promote the development of TREM2-based therapeutic strategy.
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In the citing paper
“In the healthy aging human brain, amyloid-β plaques have the ability to cause persistent inflammation in microglia, which are the brain’s resident immune cells.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [202]
Experimental — accuracy not yet measuredIn the citing paper
“TREM2 receptor interaction plays a key role in identifying microglia for the build-up of debris and damage during the regulation of microglial activation.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [202]
In the citing paper
“TREM2 agonists are being investigated as potential therapeutic agents since they reduce inflammation and encourage amyloid-beta microglial phagocytosis [202,203,204,205].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [202]
In the citing paper
“Inflammation, or neuroinflammation, is a crucial factor in the mechanisms behind AD.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [202]
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Cites
Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226
2016 Alzheimer's disease facts and figures
Alzheimer's Association (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.001 · Cited by 5,069
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089 · cited 1×
“Moreover, TREM2 combined with complement proteins, in particular C1q and C3 [93], promoting synaptic elimination of inappropriate connections during mature neural circuit refinement [94].”
BackgroundTREM2 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
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
Lane, C. A., Hardy, J., & Schott, J. M. (2018) · European Journal of Neurology · doi:10.1111/ene.13439 · Cited by 2,616
Variant of TREM2 Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558
Bloom (2014) · doi:10.1001/jamaneurol.2013.5847 · Cited by 2,194
Immune attack: the role of inflammation in Alzheimer disease
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3880 · Cited by 2,134
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
Cited by
Sorted by citations
Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease
Al-Ghraiybah, N. F., Wang, J., Alkhalifa, A. E., Roberts, A. B., Raj, R., Yang, E., & Kaddoumi, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810572 · Cited by 217
Haure-Mirande, J.-V., Audrain, M., Ehrlich, M. E., & Gandy, S. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00552-w · Cited by 159
Zhang, S., Zhu, L., Peng, Y., Zhang, L., Chao, F., Jiang, L. H., Xiao, Q., Liang, X., Tang, J., Yang, H., et al. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02401-5 · Cited by 143
Soluble TREM2: Innocent bystander or active player in neurological diseases?
Filipello, F., Goldsbury, C., You, S. F., Locca, A., Karch, C. M., & Piccio, L. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105630 · Cited by 134
Gong, S., Zhai, M., Shi, J., Yu, G., Lei, Z., Shi, Y., Zeng, Y., Ju, P., Yang, N., Zhang, Z., et al. (2024) · Cell Death and Differentiation · doi:10.1038/s41418-023-01252-8 · Cited by 129
Metadata
- Authors
- Yang, J., Fu, Z., Zhang, X., Xiong, M., Meng, L., & Zhang, Z.
- Affiliations
- Renmin Hospital of Wuhan University (CN)
- Corresponding author
- Zhang, Zhentao
- Venue
- Journal of Neuroinflammation
- Published
- 2020-07-07
- Volume
- 17
- Issue
- 1
- Pages
- 204-204
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC7341574
- OpenAlex
- W3039674883
- Cited by
- 113
- References
- 129
- Citations by year
- 2026: 12 · 2025: 11 · 2024: 32 · 2023: 23 · 2022: 19 · 2021: 16
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (No.81822016,81771382, and 81571249)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- TREM2, soluble TREM2, Alzheimer's disease, microglia, extracellular domain, cerebrospinal fluid biomarkers, tau protein, early diagnosis, neuroinflammation
- MeSH terms
- Alzheimer Disease, Animals, Humans, Membrane Glycoproteins, Receptors, Immunologic, Solubility, Biomarkers, tau Proteins, Microglia, Protein Isoforms
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