TREM2 variants and risk of Alzheimer’s disease: a meta-analysis
Abstract
Recent studies show that heterozygous variant of triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk of Alzheimer's disease (AD) but with inconclusive results. Here, we conducted a meta-analysis to summarize and clarify the association between TREM2 variants and AD, and examined the relationship between TREM2 genetic variant and the etiology of AD. Relevant case-control studies were retrieved and collected according to established inclusion criteria. Odds ratio (OR) and 95% confidence interval (95% CI) were used to estimate the associations between three TREM2 variants (rs75932628, rs104894002, and rs143332484) and AD. In overall meta-analysis, the summary ORs for rs75932628, rs104894002, and rs143332484 were 2.70 [95% CI: 2.24, 3.24; P < 0.001], 7.21 (95% CI: 1.28, 40.78; P = 0.025), and 1.65 (95% CI: 1.24, 2.21; P = 0.001), respectively, indicating that the TREM2 rs75932628, rs104894002, and rs143332484 may contribute to AD risk. However, sensitivity analysis showed that the results of rs104894002 and rs143332484 should be interpreted with caution, and larger sample size, particularly in different ethnicities, are needed to validate the two variants. The current meta-analysis demonstrates that TREM2 is a candidate gene for AD susceptibility, and TREM2 variant rs75932628 may be a risk factor for AD.
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Several AD risk-increasing variants in TREM2, such as R47H and R62H, have been recognized.
“In TREM2 gene, several AD associated risk increasing variants have been recognized, such as R47H and R62H [1, 13–15].”
From Protective PLCG2 variants associate with a delayed onset of Alzheimer’s disease among heterozygous APOE ε4 carriers (2026) · cites this paper as [14]
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Coding variants in TREM2 increase risk for Alzheimer's disease
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“reported that TREM2 R47H mutation was associated with increased density of SPs and NFTs in multiple brain regions, as well as upregulation of proinflammatory cytokines [34].”
BackgroundThe innate immune system in Alzheimer's disease
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“Its functional role in AD and other neurodegenerative diseases, although not without controversy, has been thoroughly investigated and reviewed [12, 33, 34].”
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“Given that APOE ε4 is the most well know genetic risk factor for AD, it is important to understand its complex interactions with other genetic variants, including TREM2 and PLCG2 , when considering new therapies for AD [13, 14, 42].”
- Authors
- Lu, Y., Liu, W., & Wang, X.
- Affiliations
- Tongji Hospital (CN)
- Corresponding author
- Wang, Xiong
- Venue
- Neurological Sciences
- Published
- 2015-06-03
- Volume
- 36
- Issue
- 10
- Pages
- 1881-1888
- ISSN
- 1590-1874 (ISSN-L)
- 1590-3478
- OpenAlex
- W634218667
- Cited by
- 37
- References
- 5
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 2 · 2019: 8 · 2018: 2 · 2017: 9 · 2016: 1 · 2015: 1
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neurological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- TREM2, Alzheimer's disease, genetic susceptibility, single nucleotide polymorphisms, candidate genes, disease risk
- MeSH terms
- Alzheimer Disease, Humans, Membrane Glycoproteins, Receptors, Immunologic, Genetic Variation, Genetic Predisposition to Disease
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