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Cited by 94Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

TREM2 in Alzheimer’s Disease: Microglial Survival and Energy Metabolism

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Zheng, Honghua, Cheng, Baoying, Li, Yanfang, Li, Xin, Chen, Xiaofen, Zhang, Yun-wu·2018·Frontiers in Aging Neuroscience
DOI 10.3389/fnagi.2018.00395PMC PMC6265312
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Abstract

Alzheimer's disease (AD) is the leading cause of age-related dementia among the elderly population. Recent genetic studies have identified rare variants of the gene encoding the triggering receptor expressed on myeloid cells-2 (TREM2) as significant genetic risk factors in late-onset AD (LOAD). TREM2 is specifically expressed in brain microglia and modulates microglial functions in response to key AD pathologies such as amyloid-β (Aβ) plaques and tau tangles. In this review article, we discuss recent research progress in our understanding on the role of TREM2 in microglia and its relevance to AD pathologies. In addition, we discuss evidence describing new TREM2 ligands and the role of TREM2 signaling in microglial survival and energy metabolism. A comprehensive understanding of TREM2 function in the pathogenesis of AD offers a unique opportunity to explore the potential of this microglial receptor as an alternative target in AD therapy.

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  • Many of these genes act together in distinct signalling pathways and TREM2 and PLCγ2 interact in the same cascade to modulate microglial migration, phagocytosis, and survival.

    “Many of these genes act together in distinct signalling pathways and, of note, TREM2 and PLCγ2 interact in the same cascade (Fig. 1) to modulate microglial migration, phagocytosis, and survival [34, 94].”

    From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [94]

    The Genetics of AD section names PLCG2 and TREM2 among genes associated with AD, and the TREM2 and Microglial Survival section links TREM2 to microglial migration, phagocytosis, and survival. Neither section establishes that TREM2 and PLCγ2 interact in the same signalling cascade to modulate those functions. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • About 75% of mutations in PLCG2 previously implicated in various inflammatory diseases map to the autoinhibitory interface on the PLCγ2 model structure and can be considered pathogenic.

    “A number of mutations in PLCG2 (about 75%), that have been previously implicated in various inflammatory diseases [92–102], actually map to the autoinhibitory interface on the PLCγ2 model structure and can be considered as pathogenic (Fig. 2c)”

    From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [94]

    The Genetics of AD section mentions PLCG2 among genes with rare variants associated with Alzheimer’s disease risk. It does not address the claimed 75% figure, inflammatory-disease mutations, their location on a PLCγ2 autoinhibitory interface, or their pathogenicity; searches for those terms found no supporting passage in our copy. (LLM, conf=0.76)

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Authors
Zheng, H., Cheng, B., Li, Y., Li, X., Chen, X., & Zhang, Y.-W.
Affiliations
Xiamen University (CN)
Corresponding author
Zheng, Honghua
ORCID
Venue
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Published
2018-11-23
Volume
10
Pages
395-395
ISSN
1663-4365 (ISSN-L)
DOI
10.3389/fnagi.2018.00395
PMC
PMC6265312
OpenAlex
W2900949825
Cited by
94
References
152
Citations by year
2026: 7 · 2025: 9 · 2024: 9 · 2023: 11 · 2022: 13 · 2021: 20 · 2020: 17 · 2019: 7 · 2017: 1
FWCI
4.95
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Aging Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National Natural Science Foundation of China
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
TREM2, Alzheimer's disease, microglia, microglial survival, TREM2 signaling, amyloid plaques, tau tangles, late-onset Alzheimer's disease, genetic risk factors, therapeutic target

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