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TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer's Disease.TREM2 在调节阿尔茨海默病小胶质细胞病理中的作用位于 CD33 下游。
Neuron. 2019 Sep 4;103(5):820-835.e7. doi: 10.1016/j.neuron.2019.06.010. Epub 2019 Jul 10.
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Microglial mTOR Activation Upregulates Trem2 and Enhances β-Amyloid Plaque Clearance in the Alzheimer's Disease Model.小胶质细胞 mTOR 激活上调 Trem2 并增强阿尔茨海默病模型中的β-淀粉样斑块清除。
J Neurosci. 2022 Jul 6;42(27):5294-5313. doi: 10.1523/JNEUROSCI.2427-21.2022. Epub 2022 Jun 7.
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Prior activation state shapes the microglia response to antihuman TREM2 in a mouse model of Alzheimer's disease.预先激活状态塑造了小胶质细胞对阿尔茨海默病小鼠模型中抗人 TREM2 的反应。
Proc Natl Acad Sci U S A. 2021 Jan 19;118(3). doi: 10.1073/pnas.2017742118.
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Gene therapy for Alzheimer's disease targeting CD33 reduces amyloid beta accumulation and neuroinflammation.针对 CD33 的阿尔茨海默病基因治疗可减少淀粉样β聚集和神经炎症。
Hum Mol Genet. 2020 Oct 10;29(17):2920-2935. doi: 10.1093/hmg/ddaa179.
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Curcumin restores innate immune Alzheimer's disease risk gene expression to ameliorate Alzheimer pathogenesis.姜黄素恢复先天免疫阿尔茨海默病风险基因表达，改善阿尔茨海默病发病机制。
Neurobiol Dis. 2019 Jul;127:432-448. doi: 10.1016/j.nbd.2019.02.015. Epub 2019 Apr 2.
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Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model.Trem2 缺失减少晚期淀粉样斑块积累，增加 Aβ42:Aβ40 比值，并加重 PS2APP 阿尔茨海默病小鼠模型的轴突变性和树突棘丢失。
J Neurosci. 2020 Feb 26;40(9):1956-1974. doi: 10.1523/JNEUROSCI.1871-19.2019. Epub 2020 Jan 24.
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Intermittent hypoxia training enhances Aβ endocytosis by plaque associated microglia via VPS35-dependent TREM2 recycling in murine Alzheimer's disease.间歇性低氧训练通过 VPS35 依赖性 TREM2 循环利用增强斑块相关小胶质细胞对 Aβ 的内吞作用，从而改善阿尔茨海默病模型小鼠的认知功能。
Alzheimers Res Ther. 2024 Jun 3;16(1):121. doi: 10.1186/s13195-024-01489-6.
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TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques.TREM2介导的早期小胶质细胞反应限制了淀粉样斑块的扩散和毒性。
J Exp Med. 2016 May 2;213(5):667-75. doi: 10.1084/jem.20151948. Epub 2016 Apr 18.
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Alzheimer's disease associated isoforms of human CD33 distinctively modulate microglial cell responses in 5XFAD mice.人类 CD33 的阿尔茨海默病相关亚型可显著调节 5XFAD 小鼠小神经胶质细胞的反应。
Mol Neurodegener. 2024 May 27;19(1):42. doi: 10.1186/s13024-024-00734-8.
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Effects of microglial depletion and TREM2 deficiency on Aβ plaque burden and neuritic plaque tau pathology in 5XFAD mice.小胶质细胞耗竭和 TREM2 缺失对 5XFAD 小鼠 Aβ斑块负担和神经突斑块 tau 病理的影响。
Acta Neuropathol Commun. 2021 Sep 9;9(1):150. doi: 10.1186/s40478-021-01251-1.
引用本文的文献
1
MicroRNA-429 Inhibits Microglial Inflammation by Targeting Through the NF-κB Pathway.微小RNA-429通过NF-κB途径靶向抑制小胶质细胞炎症。
Mediators Inflamm. 2025 Jul 24;2025:7165782. doi: 10.1155/mi/7165782. eCollection 2025.
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Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review).小胶质细胞中的脂质代谢：神经退行性疾病的新机制与治疗机遇（综述）
Int J Mol Med. 2025 Sep;56(3). doi: 10.3892/ijmm.2025.5580. Epub 2025 Jul 11.
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Association of CD33 genetic variants with neurocognitive profiles in chronic viral hepatitis.慢性病毒性肝炎中CD33基因变异与神经认知特征的关联
BJPsych Open. 2025 Jul 10;11(4):e147. doi: 10.1192/bjo.2025.10048.
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Innate Immune Mechanisms in the Central Nervous System.中枢神经系统中的固有免疫机制
Adv Exp Med Biol. 2025;1476:381-409. doi: 10.1007/978-3-031-85340-1_15.
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Immune cells in Alzheimer's disease: insights into pathogenesis and potential therapeutic targets.阿尔茨海默病中的免疫细胞：对发病机制和潜在治疗靶点的见解
Med Rev (2021). 2024 Dec 23;5(3):179-202. doi: 10.1515/mr-2024-0064. eCollection 2025 Jun.
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Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside Applications.健康与疾病中的巨噬细胞信号通路：从实验室到临床应用
MedComm (2020). 2025 Jun 16;6(7):e70256. doi: 10.1002/mco2.70256. eCollection 2025 Jul.
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Alzheimer's disease pathogenesis: standing at the crossroad of lipid metabolism and immune response.阿尔茨海默病发病机制：处于脂质代谢与免疫反应的十字路口
Mol Neurodegener. 2025 Jun 4;20(1):67. doi: 10.1186/s13024-025-00857-6.
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Hampered AMPK-ULK1 cascade in Alzheimer's disease (AD) instigates mitochondria dysfunctions and AD-related alterations which are alleviated by metformin.阿尔茨海默病（AD）中受阻碍的AMPK-ULK1级联反应引发线粒体功能障碍和AD相关改变，而二甲双胍可缓解这些改变。
Alzheimers Res Ther. 2025 Jun 2;17(1):127. doi: 10.1186/s13195-025-01772-0.
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Unraveling the complex role of microglia in Alzheimer's disease: amyloid β metabolism and plaque formation.解析小胶质细胞在阿尔茨海默病中的复杂作用：淀粉样β蛋白代谢与斑块形成
Inflamm Regen. 2025 May 30;45(1):16. doi: 10.1186/s41232-025-00383-4.
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GADD45G operates as a pathological sensor orchestrating reactive gliosis and neurodegeneration.GADD45G作为一种病理传感器，协调反应性胶质增生和神经退行性变。
Neuron. 2025 Jul 9;113(13):2176-2195.e10. doi: 10.1016/j.neuron.2025.04.033. Epub 2025 May 22.
本文引用的文献
1
High-affinity interactions and signal transduction between Aβ oligomers and TREM2.Aβ寡聚体与 TREM2 之间的高亲和力相互作用和信号转导。
EMBO Mol Med. 2018 Nov;10(11). doi: 10.15252/emmm.201809027.
2
Amyloid-beta modulates microglial responses by binding to the triggering receptor expressed on myeloid cells 2 (TREM2).淀粉样蛋白-β通过与髓样细胞表达的触发受体 2（TREM2）结合来调节小胶质细胞的反应。
Mol Neurodegener. 2018 Mar 27;13(1):15. doi: 10.1186/s13024-018-0247-7.
3
Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity and Ameliorates Pathological Phenotypes in Alzheimer's Disease Models.TREM2 基因剂量升高可重塑小胶质细胞的反应性并改善阿尔茨海默病模型的病理表型。
Neuron. 2018 Mar 7;97(5):1032-1048.e5. doi: 10.1016/j.neuron.2018.02.002.
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TREM2 Is a Receptor for β-Amyloid that Mediates Microglial Function.TREM2 是 β-淀粉样蛋白的受体，可介导小胶质细胞的功能。
Neuron. 2018 Mar 7;97(5):1023-1031.e7. doi: 10.1016/j.neuron.2018.01.031.
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Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism.人源化 Trem2 小鼠揭示了 R47H 多态性的小胶质细胞内在和外在作用。
J Exp Med. 2018 Mar 5;215(3):745-760. doi: 10.1084/jem.20171529. Epub 2018 Jan 10.
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Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions.多发性硬化症病理学的基因表达谱分析确定了慢性活动性病变周围脱髓鞘的早期模式。
Front Immunol. 2017 Dec 21;8:1810. doi: 10.3389/fimmu.2017.01810. eCollection 2017.
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Microglia in Alzheimer's disease.阿尔茨海默病中的小胶质细胞。
J Cell Biol. 2018 Feb 5;217(2):459-472. doi: 10.1083/jcb.201709069. Epub 2017 Dec 1.
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TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy.TREM2 缺乏可减轻神经炎症并预防神经退行性变tau 病模型中的小鼠。
Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11524-11529. doi: 10.1073/pnas.1710311114. Epub 2017 Oct 9.
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The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases.TREM2-载脂蛋白E通路驱动神经退行性疾病中功能失调的小胶质细胞的转录表型。
Immunity. 2017 Sep 19;47(3):566-581.e9. doi: 10.1016/j.immuni.2017.08.008.
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Increased peripheral blood inflammatory cytokine levels in amyotrophic lateral sclerosis: a meta-analysis study.肌萎缩侧索硬化症患者外周血炎症细胞因子水平升高：一项荟萃分析研究。
Sci Rep. 2017 Aug 22;7(1):9094. doi: 10.1038/s41598-017-09097-1.
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