The role of TREM2 in Alzheimer’s disease: from the perspective of Tau
Open accessAbstract
Triggering receptor expressed on myeloid cells 2 (TREM2), a pattern recognition receptor abundantly expressed on microglia, has been identified as one of the risk factors for Alzheimer’s disease (AD). Several studies have already demonstrated the relationship between TREM2 and Tau. TREM2 mutations and altered expression play an important role in Tau phosphorylation. Furthermore, the level of Tau phosphorylation is correlated with soluble TREM2 (sTREM2). However, in different stages of AD, TREM2 seems to have varying effects on Tau pathology. The explicit interaction between TREM2 and Tau, as well as how they affect AD pathology, remains unclear, and there is much evidence to the contrary that requires rational interpretation. Reviewing the dual roles of TREM2 in AD will help identify a more appropriate development strategy for targeting TREM2 to treat AD. Therefore, this review focuses on the interplay between Tau and TREM2 in relation to AD.
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TREM2-related microglial activation may support amyloid plaque engagement.
“TREM2-related microglial activation may support amyloid plaque engagement”
From Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis? (2026) · cites this paper as [55]
Pathways that support amyloid plaque response may have different consequences in tau-rich or late-stage disease.
“pathways that support amyloid plaque response may have different consequences in tau-rich or late-stage disease [55,60]”
From Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis? (2026) · cites this paper as [55]
The role of TREM2-related microglial activation in tau-dominant or later-stage disease is more controversial.
“its role in tau-dominant or later-stage disease is more controversial”
From Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis? (2026) · cites this paper as [55]
Inflammation, or neuroinflammation, is a crucial factor in the mechanisms behind AD.
“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 [203]
TREM2 receptor interaction plays a key role in identifying microglia for the build-up of debris and damage during the regulation of microglial activation.
“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 [203]
In the healthy aging human brain, amyloid-β plaques have the ability to cause persistent inflammation in microglia.
“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 [203]
TREM2 agonists are being investigated as potential therapeutic agents because they reduce inflammation and encourage amyloid-beta microglial phagocytosis.
“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 [203]
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BackgroundSoluble TREM2 levels associate with conversion from mild cognitive impairment to Alzheimer’s disease
Zhao, A., Jiao, Y., Ye, G., Kang, W., Tan, L., Li, Y., Deng, Y., & Liu, J. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158708 · Cited by 70 · see citing works
Peng, X., Guo, H., Zhang, X., Yang, Z., Ruganzu, J. B., Yang, Z., Wu, X., Bi, W., Ji, S., & Yang, W. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03217-x · Cited by 69 · see citing works
Nasu‐Hakola disease: The first case reported by Nasu and review
Kaneko, M., Sano, K., Nakayama, J., & Amano, N. (2010) · Neuropathology · doi:10.1111/j.1440-1789.2010.01127.x · Cited by 67 · see citing works
Biel, D., Suárez‐Calvet, M., Hager, P., Rubinski, A., Dewenter, A., Steward, A., Roemer, S. N., Ewers, M., Haass, C., Brendel, M., et al. (2023) · EMBO Molecular Medicine · doi:10.15252/emmm.202216987 · Cited by 55 · see citing works
Knapskog, A., Henjum, K., Idland, A., Eldholm, R. S., Persson, K., Saltvedt, I. T., Watne, L. O., Engedal, K., & Nilsson, L. N. G. (2020) · Scientific Reports · doi:10.1038/s41598-020-72878-8 · Cited by 51 · see citing works
Multicenter Alzheimer's and Parkinson's disease immune biomarker verification study
Brosseron, F., Kolbe, C., Santarelli, F., Carvalho, S., Antonell, A., Castro‐Gomez, S., Tacik, P., Namasivayam, A. A., Mangone, G., Schneider, R., et al. (2020) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2019.07.018 · Cited by 47 · see citing works
Singh, A. K., Mishra, G., Maurya, A., Awasthi, R., Kumari, K., Thakur, A., Rai, A., Rai, G. K., Sharma, B., Kulkarni, G. T., et al. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190903102822 · Cited by 45 · see citing works
Plasma soluble TREM2 is associated with white matter lesions independent of amyloid and tau
Tsai, H.-H. C., Chen, Y., Yen, R., Lo, Y.-L., Yang, K., Jeng, J., Tsai, L., & Chang, C.-F. (2021) · Brain · doi:10.1093/brain/awab332 · Cited by 45 · cited 1× · see citing works
“Existing studies show that this association with AD is re fl ected in the CSF rather than plasma (Piccio et al., 2016). sTREM2 in plasma may be associated with other diseases, such as white matter lesions (Tsai et al., 2021).”
BackgroundTherapeutic Effect of Modulating TREM-1 via Anti-inflammation and Autophagy in Parkinson’s Disease
Feng, C., Chen, N., Sung, C., Kuo, H., Yang, S., Chen, C., Hung, H.-C., Chen, B., Wen, Z., & Chen, W.-F. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00769 · Cited by 43 · see citing works
Li, R., Wang, X., & He, P. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.9778 · Cited by 39 · cited 2× · see citing works
“The R47H variant is associated with a reduction in the number of receptors, loss of function, and potentially an earlier onset of AD (Li et al., 2021).”
BackgroundSekiya, M., Wang, M., Fujisaki, N., Sakakibara, Y., Quan, X., Ehrlich, M. E., De Jager, P. L., Bennett, D. A., Schadt, E. E., Gandy, S., et al. (2018) · Genome Medicine · doi:10.1186/s13073-018-0530-9 · Cited by 38 · see citing works
Winfree, R. L., Seto, M., Dumitrescu, L. C., Menon, V., Jager, P. L. D., Wang, Y., Schneider, J. A., Bennett, D. A., Jefferson, A. L., & Hohman, T. J. (2023) · Acta Neuropathologica · doi:10.1007/s00401-023-02564-2 · Cited by 38 · see citing works
Bac, B., Hicheri, C., Weiss, C., Buell, A., Vilcek, N., Späni, C. B., Geula, C., Savas, J. N., & Disterhoft, J. F. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.12.015 · Cited by 31 · see citing works
Qin, Q., Wan, H., Wang, D., Li, J., Qu, Y., Zhao, J., Li, J., & Xue, Z. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.892493 · Cited by 29 · see citing works
Microglia and microglial-based receptors in the pathogenesis and treatment of Alzheimer’s disease
Wang, Z., & Weaver, D. F. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109070 · Cited by 25 · cited 2× · see citing works
“In in vivo studies, activation of TREM2 by AL002 reverses amyloid, promotes microglia recruitment, and improves neurological function (Wang and Weaver, 2022).”
BackgroundEmerging Roles of Cells and Molecules of Innate Immunity in Alzheimer’s Disease
Tamburini, B., Badami, G. D., Manna, M. P. L., Azgomi, M. S., Caccamo, N., & Dieli, F. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241511922 · Cited by 22 · cited 2× · see citing works
“Because TREM2 can recognize a variety of ligands closely related to AD and is one of the key regulators of microglial phenotype switching, it plays an important role in the progression of neuroin fl ammation (Tamburini et al., 2023).”
BackgroundZhang, B., Li, R. Q., Zhang, Y., & Gao, X. (2020) · Medicine · doi:10.1097/md.0000000000018921 · Cited by 20 · see citing works
TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo
Lee-Gosselin, A., Jury-Garfe, N., You, Y., Dabin, L., Soni, D., Dutta, S., Rochet, J.-C., Kim, J., Oblak, A. L., & Lasagna-Reeves, C. A. (2023) · Cells · doi:10.3390/cells12121597 · Cited by 19 · see citing works
Gussago, C., Casati, M., Ferri, E., & Arosio, B. (2019) · The Journal of Frailty & Aging · doi:10.14283/jfa.2018.43 · Cited by 17 · see citing works
Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2
Ogonowski, N. S., Santamaría‐García, H. A., Báez, S., López, A., Laserna, A., Garcia-Cifuentes, E. R., Ayala‐Ramírez, P., Zarante, I., Suárez‐Obando, F., Reyes, P. A., et al. (2023) · Journal of Medical Genetics · doi:10.1136/jmg-2022-108627 · Cited by 10 · see citing works
Do Alzheimer's Disease Risk Gene Products Actually Act in Microglia?
Hashioka, S., Inoue, K., Takeshita, H., & Inagaki, M. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.589196 · Cited by 9 · see citing works
Ni, J.-W., Li, C., Chen, X., & Cai, W. (2022) · Neurology India · doi:10.4103/0028-3886.364080 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
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Beyond Amyloid and Tau: The Critical Role of Microglia in Alzheimer’s Disease Therapeutics
Dias, D., & Socodato, R. (2025) · Biomedicines · doi:10.3390/biomedicines13020279 · Cited by 57 · see citing works
“It is a molecular switch that controls several microglial functions, including their survival, proliferation, activation state, and the phagocytosis of apoptotic neurons and amyloid-beta (A β ) plaques [22–24].”
InfluentialRecent Advances in Therapeutics for the Treatment of Alzheimer’s Disease
Thawabteh, A. M., Ghanem, A. W., AbuMadi, S., Thaher, D., Jaghama, W., Karaman, D., & Karaman, R. (2024) · Molecules · doi:10.3390/molecules29215131 · Cited by 56 · see citing works
TREM2 in Neurodegenerative Disorders: Mutation Spectrum, Pathophysiology, and Therapeutic Targeting
Yang, H.-W., Kim, D., Yang, Y., Bagyinszky, E., & An, S. S. A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26157057 · Cited by 25 · see citing works
“Although partial or normal TREM2 activity was suggested to contribute to Tau disease or Tau-mediated damage, the full loss of TREM2 function could alleviate the Tau-mediated neuronal damage [125–127].”
Decoding NLRP3 Inflammasome Activation in Alzheimer’s Disease: A Focus on Receptor Dynamics
Maurya, R., Sharma, A., & Naqvi, S. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04918-1 · Cited by 20 · see citing works
“Among the various receptors that influence NLRP3 activation, TREM2 has garnered significant attention due to its regulatory role in microglial function and its strong genetic association with Alzheimer’s disease risk [91, 92].”
Wang, D., Liu, J., Zhu, Q., Wei, X., Zhang, X., Chen, Q., Zhao, Y., Tang, H., & Xu, W. (2024) · Nutrients · doi:10.3390/nu16203558 · Cited by 17 · see citing works
“These processes influence various physiological functions of microglia, including metabolism, proliferation, cytokine release, phagocytosis, and migration [54–57].”
BackgroundUnraveling the Immune Puzzle: Role of Immunomodulation in Alzheimer’s Disease
Ashvin, Dhapola, R., Kumari, S., Sharma, P., Vellingiri, B., Medhi, B., & HariKrishnaReddy, D. (2025) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-025-10210-9 · Cited by 17 · see citing works
“TREM 2 is important for inhibiting microglial apoptosis, pyroptosis, and promoting microglial proliferation (Jurcău et al. 2022; Huang et al. 2023 ).”
Farzan, M., Rounkian, M. S., Rizi, A. A., Heidari, Z., Farzan, M., Fathi, M., Aghaei, A., Azadegan‐Dehkordi, F., & Bagheri, N. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.115071 · Cited by 14 · see citing works
Immunosenescence and the Geriatric Giants: Molecular Insights into Aging and Healthspan
Fetarayani, D., Kahdina, M., Waitupu, A., Pratiwi, L., Ningtyas, M. C., Adytia, G. J., & Sutanto, H. (2025) · Medical Sciences · doi:10.3390/medsci13030100 · Cited by 14 · see citing works
“Importantly, genetic studies have identified variants in microglial genes such as TREM2 , which impair A β clearance and increase the AD risk [173,174].”
Ferroptosis in Alzheimer’s disease: molecular mechanisms and advances in therapeutic strategies
Zhou, Z., Zhang, Y., Liu, S., Tang, H., Yang, L., Lu, Y., Liao, J., Zhang, S., Chen, Z., & Yang, L. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1673315 · Cited by 14 · see citing works
“These interventions have shown potential in improving AD-related cognitive impairment (Huang et al., 2023; Melchiorri et al., 2023).”
Huang, L.-T., Liu, M., Li, Z., Li, B., Wang, J., & Zhang, K. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00865 · Cited by 12 · see citing works
“TREM2 is a single transmembrane protein that can recognize Aβ and stimulate its phagocytosis by microglia (Doens et al., 2014; Zhao et al., 2018; Qin et al., 2022; Huang et al., 2023; Zgorzynska et al., 2024).”
A philosophy of science approach to the amyloid hypothesis of Alzheimer's disease
Daly, T. P. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16500 · Cited by 12 · see citing works
“Important genes involved are those with roles in the amyloid/tau pathways, cholesterol metabolism, and immune function (Huang et al., 2023).”
Trivedi, N., Bhosale, J. D., Pant, A. M., Suryawanshi, S. P., Tiwari, P., Abel, P. W., & Jadhav, G. P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262110386 · Cited by 11 · see citing works
“It enhances phagocytosis and suppresses pro-inflammatory signaling, contributing to neuroprotection in disorders like Alzheimer’s disease [14,15].”
Huang, W., Huang, J., Kuang, N., Wu, J., Feng, F., Luo, Y., & Huang, N. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103290 · Cited by 12 · see citing works
Self-citationNovel insights into the role of TREM2 in cerebrovascular diseases
Awuah, W. A., Ben-Jaafar, A., Kong, J. S. H., Sanker, V., Shah, M. H., Poornaselvan, J., Frimpong, M., Imran, S., Alocious, T., Abdul-Rahman, T., et al. (2024) · Brain Research · doi:10.1016/j.brainres.2024.149245 · Cited by 10 · see citing works
Azizan, Z., Bazrgar, M., Bazgir, N., Moini, S. H., Ghaseminejad‐Kermani, S., Safa, K., Eshaghian‐dorcheh, A., & Harirchian, M. H. (2025) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70269 · Cited by 10 · see citing works
“Remarkably, research indicates that the receptor TREM2 may mitigate synaptic loss by binding to C1q, thus preventing excessive complement activation and subsequent synaptic elimination [42].”
The role of AMPKα subunit in Alzheimer's disease: In-depth analysis and future prospects
Xia, L., Chen, J., Huang, J., Lin, X., Jiang, J., Liu, T., Huang, N., & Luo, Y. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e34254 · Cited by 9 · see citing works
“Therefore, reducing the levels of hyperphosphorylated Tau protein could effectively alleviate AD progression [91,92].”
BackgroundSelf-citationHematopoietic stem cell gene therapy to halt neurodegeneration
Biffi, A. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00440 · Cited by 9 · see citing works
“Of note, individual carrying hypomorphic and hypofunctional variants in microglia-signature genes, such as TREM2, are known to be at increased risk of developing NDDs, further highlighting the role of microglia in the pathogenesis of these conditions [13].”
BackgroundWang, M., Zhang, L., Huang, W., Huang, J., Luo, Y., & Huang, N. (2025) · Complementary Therapies in Medicine · doi:10.1016/j.ctim.2025.103222 · Cited by 10 · see citing works
Self-citationMetabolic and inflammatory roles of glial cells in neurodegenerative and cerebrovascular diseases
OGUNLEYE, F. A., Zhou, Y., Yan, L., Abhulimen, P. O., Xu, Y., Lai, M. K. P., Okunowo, W. O., Sethi, G., Fang, C., & Ma, Y. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103120 · Cited by 10 · see citing works
Unveiling the impact of TREM-2+ Macrophages in metabolic disorders
Contreras, M., Matos, A. D. O., Dantas, P. H. D. S., Neto, J. R. D. C., Silva‐Sales, M., & Sales‐Campos, H. (2024) · Cellular Immunology · doi:10.1016/j.cellimm.2024.104882 · Cited by 9 · see citing works
Niazi, N. U. K., Jiang, J., Ou, H., Chen, R., & Yang, Z. (2025) · Brain Sciences · doi:10.3390/brainsci15060641 · Cited by 7 · see citing works
“Notably, a triggering receptor expressed on myeloid cell type 2 (TREM2), a microglial marker, exhibits mutations in AD patients [46].”
Wang, Y., Wang, Z., Hao, H., Zhao, Y., Wang, J., & Wang, W. (2025) · Toxics · doi:10.3390/toxics13010037 · Cited by 7 · see citing works
“TREM2 is a cell surface receptor mainly expressed in microglia of the CNS, and full-length TREM2 contains 230 amino acids [9].”
Wang, F., Liang, Y., & Wang, Q. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01646-x · Cited by 7 · see citing works
“Studies have identified the transmembrane protein TREM2 as a significant risk gene implicated in AD pathogenesis [47].”
TREM2 and LAG-3 in cancer and Alzheimer’s disease immunotherapy
Yuan, S., Fuchs, N. S., Abdel‐Rahman, S. A., Kaur, B., & Gabr, M. T. (2025) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2025.06.010 · Cited by 6 · see citing works
Kordi, R., Andrews, T. J., & Hicar, M. D. (2025) · Virology · doi:10.1016/j.virol.2025.110523 · Cited by 6 · see citing works
Microglia protein profiles in CSF across Alzheimer’s disease clinical stages
Blujdea, E. R., van Bokhoven, P., Adami, P. V. M., Marshe, V. S., Vromen, E., Hok‐A‐Hin, Y. S., Boiten, W. A., Irwin, D. J., Chen‐Plotkin, A. S., Lemstra, A. W., et al. (2026) · Nature Aging · doi:10.1038/s43587-026-01088-0 · Cited by 7 · see citing works
“26–30), MIF 27 and sAXL 10 , that are elevated in earlier stages of AD, possibly as a protective response to the accumulation of amyloid pathology 10,25,28,31–33 .”
Wu, J., Ge, Y., Zhang, L., Huang, J., Huang, N., & Luo, Y. (2026) · Stem Cell Research & Therapy · doi:10.1186/s13287-026-04954-1 · Cited by 5 · see citing works
“The systematic detection of tau protein phosphorylation levels, which is among the core pathological features of AD [41], also needs to be performed to help clarify the potential impact of treatment measures on the formation of neurofibrillary tangles.”
Self-citationChan, C. C., Lam, K. K., Chen, L., Yu, M., Hu, J., Zhu, Y., Zheng, Y., Zheng, J., Choy, K. W., & Dong, Z. (2025) · Science China Life Sciences · doi:10.1007/s11427-025-3083-8 · Cited by 5 · see citing works
Guo, F., Tan, M., Hu, H., Ou, Y., Zhang, M., Sheng, Z.-H., Chi, H., Tan, L., & Initiative, A. D. N. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-240372 · Cited by 4 · see citing works
“48 TREM2-activating antibodies can enhance microglial migration towards amyloid plaques, promote phagocytosis, reduce endogenous tau hyperphosphorylation, and improve cognitive function.”
Body Composition and Alzheimer’s Disease: A Holistic Review
Frank, G., Gualtieri, P., Cianci, R., Caldarelli, M., Palma, R., Santis, G. D. D., Porfilio, C., Nicoletti, F., Bigioni, G., & di Renzo, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179573 · Cited by 3 · see citing works
“The role of TREM2 in complement-mediated synaptic pruning is complex, with conflicting evidence suggesting a dual effect in the context of AD [10].”
BackgroundFueling Alzheimer’s Disease: Where Does Immunometabolism Stand?
Correia, S. C., Perry, G. L., & Moreira, P. I. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-240787 · Cited by 3 · see citing works
Plasma NFL, GFAP, sTREM2, pTau231, and clinical severity in progressive supranuclear palsy
Lee, S., Kim, H., Kim, R., Jin, B., Kim, S., Ha, S. H., Shin, J. H., Jeon, B., Kim, H.-J., & Lee, J.-Y. (2025) · Journal of Neurology · doi:10.1007/s00415-025-13570-7 · Cited by 3 · see citing works
Cannabinoids in Alzheimer’s disease: animal–human evidence and clinical pharmacology challenges
Komedera, M., Wojda, U., & Kiryk, A. (2026) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2026.1833021 · Cited by 3 · see citing works
“Cannabinoids may partially counteract this process by reducing tau phosphorylation, including through mechanisms associated with lower GSK-3 β activity, and by supporting cellular pathways involved in the clearance of abnormal tau forms (Wang et al., 2022; Raïch et al., 2025; Huang et al., 2023).”
Fowler, D. K., Savage, T. M., & Mackie, D. I. (2026) · Journal of Cannabis Research · doi:10.1186/s42238-026-00445-5 · Cited by 2 · see citing works
“…spleen tyrosine kinase (SYK)-NLRP3 pathways in microglia, promoting a vicious cycle of cytokine production, impaired phagocytosis of pathological proteins, and synaptic pruning that contributes to a toxic microenvironment for vulnerable cholinergic and glutamatergic neurons (Huang et al., 2023).”
Multi-omics analysis reveals aspirin is associated with reduced risk of Alzheimer’s diseasePreprint
Grabowska, M. E., Vaidya, A. U., Zhong, X., Guardo, C., Dickson, A. L., Babanejad, M., Yan, C., Xin, Y., Mundo, S., Peterson, J. F., et al. (2025) · medRxiv · doi:10.1101/2025.04.07.25325038 · Cited by 2 · see citing works
Mainali, N., Balasubramaniam, M., Pahal, S., Griffin, W. S. T., Reis, R. J. S., & Ayyadevara, S. (2025) · Basic Research in Cardiology · doi:10.1007/s00395-025-01109-w · Cited by 1 · see citing works
“The accrual of protein aggregates in AD has historically been focused chiefly on amyloid beta and tau oligomerization; however, recent evidence suggests that other proteins may initiate or exacerbate aggregation [27, 43, 89, 90].”
Pashaei, S., Morozova‐Roche, L. A., Rahimi, Z., Mohammadi, S., Barzegari, E., Shabani, S., Salari, N., & Khodarahmi, R. (2025) · Biochemical Genetics · doi:10.1007/s10528-025-11210-3 · Cited by 1 · see citing works
“CN is a phosphatase that relies on Ca2+ and calmodulin, exhibiting high expression levels in the central nervous system (CNS).”
InfluentialCavanaugh, C., Moore, A. E., Fitz, N., Lefterov, I., & Koldamova, R. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26167849 · Cited by 2 · see citing works
Adeola, H. A., & Robinson, R. A. S. (2025) · ACS Bio & Med Chem Au · doi:10.1021/acsbiomedchemau.5c00074 · Cited by 1 · see citing works
Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis?
Chmiel, J., Gawełczyk, W., Soczyńska, J., & Leszek, J. (2026) · Cells · doi:10.3390/cells15131151
“…well: TREM2-related microglial activation may support amyloid plaque engagement, but its role in tau-dominant or later-stage disease is more controversial, and some authors have warned that timing may determine whether a microglia-targeted intervention behaves as a “friend” or a “foe” [55,56].”
Gene therapy for neurodegenration
Koduru, T. S., Osmani, R. A. M., & Madhuchandra, K. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-28822-7.00027-1
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Zachara, R., de Carrillo, D. G., Właszczuk, A., Gorzkowska, A., Mazur, W., & Jędrzejowska–Szypułka, H. (2025) · Neurology International · doi:10.3390/neurolint17110180
“The role of inflammation in AD is complicated and possibly diversified in different AD stages [16].”
Can Nutrition Modulate the Progression of Alzheimer’s Disease? A Narrative Review
Jankowski, W. M., Fichna, J., & Tarasiuk, A. (2026) · Current Nutrition Reports · doi:10.1007/s13668-026-00733-9
Actin cytoskeletal pathology in Alzheimer’s disease
Chinnathambi, S., Malik, S., Chandrashekar, M., & Rangappa, N. (2026) · Advances in pharmacology · doi:10.1016/bs.apha.2025.12.003
Nema, S., Sharma, A., Werneburg, S., Singh, A., & Singh, Y. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-33623-2.00014-3
ARID5A RNA-binding coordinates microglial defense and ferroptosis in iPSC-derived models
Schafer, D. M., Blue, S. M., Xu, S., Mizrahi, O., Gosztyla, M. L., Street, L., Rothamel, K. L., Kopalle, H., Landry, S. B., Rosales, E. K. F., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-76131-0
“The T66M variant is characterized by rampant neuroin fl ammation, dysregulated iron metabolism 74 , and de fi cits in microglial activity and phagocytic capability 72,74 – 76 .”
Endolysosomal pathway and autophagy dysregulation in Alzheimer’s disease
Singh, A., Gulati, I., Darshna, D., & Tiwari, S. S. (2026) · International review of neurobiology · doi:10.1016/bs.irn.2026.08.002
Sleep and stress as modifiable drivers of Alzheimer’s disease
Wear, D., Hussaini, S. A., & Yu, W. H. (2026) · npj Dementia · doi:10.1038/s44400-026-00127-2
TREM2-directed therapy in Alzheimer’s disease: from therapeutic window to clinical translation
Kuang, Q., Li, S., Huang, W., Kuang, N., Liu, T., Huang, N., Luo, Y., & Huang, J. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1938062
“Compared with amyloid pathology, the role of TREM2 in tau-driven neurodegeneration appears more context dependent and should be interpreted with greater caution (Huang et al., 2023).”
Self-citation
- Authors
- Huang, W., Huang, J., Huang, N., & Luo, Y.
- Affiliations
- Zunyi Medical University (CN)
- Corresponding author
- Huang, Nanqu
- Luo, Yong
- Venue
- Frontiers in Cell and Developmental Biology
- Publisher
- Frontiers Media SA
- Published
- 2023-11-08
- Volume
- 11
- Pages
- 1280257-1280257
- ISSN
- 2296-634X (ISSN-L)
- PMC
- PMC10663217
- OpenAlex
- W4388523561
- Cited by
- 49
- References
- 88
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 12
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cell and Developmental Biology (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
- Guizhou Science and Technology Department
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- TREM2, Alzheimer's disease, tau protein, tau phosphorylation, soluble TREM2, microglia, pattern recognition receptors, neuroinflammation
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