The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
The triggering receptor expressed on myeloid cells 2 ( TREM2 ) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia
Open accessAbstract
Introduction: The objective of this study was to elucidate the relationship between the triggering receptor expressed on myeloid cells 2 ( TREM2 ) risk variant, neuropathological lesions, alterations in gene and protein expression, and the severity of neuroinflammation. Methods: The genetic association study of the R47 H TREM2 variant with Alzheimer's disease (AD), neuropathology, and changes in TREM2 and TYRO protein tyrosine kinase‐binding protein ( TYROBP) gene and protein expression, and neuroinflammatory markers. Results: The TREM2 variant is associated with: (i) AD (odds ratio: 4.76; P = .014); (ii) increased density of amyloid plaques and neurofibrillary tangles in multiple brain regions; (iii) increased TREM2 ( P = .041) and TYROBP ( P = .006) gene expression; (iv) decreased TREM2 protein levels ( P = .016); and (v) upregulation of proinflammatory cytokines (regulated on activation, normal T cell expressed and secreted [RANTES] and interferon [IFN] gamma) ( P = .003) and nominal downregulation of protective markers (α2‐macroglobulin, interleukin 4 or IL‐4, and ApoA1) ( P = .018). Discussion: These findings link the TREM2 missense mutation with specific molecular abnormalities and increases in neuropathological lesions in the human brain.
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“They also reported higher TREM2 gene expression in AD R47H carriers relative to controls and no difference in TREM2 between AD noncarriers and control.”
From Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review (2018) · cites this paper as [107]
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“Their protein measurements, however, indicated decreased TREM2 in AD R47H carriers relative to controls with no difference between AD noncarriers and control.”
From Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review (2018) · cites this paper as [107]
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“Several other TREM2 variants that affect the expression of TREM2 also increased the risk of AD, including R62H, T66M, H157Y, and D87N.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [165]
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Items 101–105 of 105
Lietzke, E. E., Saeb, D., Aldrich, E. C., de Menezes, R. F., Bruce, K. D., & Sprenger, K. G. (2026) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2026.06.002 · Cited by 1
Yang, G., Xu, X., & Xu, Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1893545
The Crosstalk Between Diabetes and Alzheimer's Disease: A Molecular Perspective
Çataklı, D., Özen, Ö., Tuncgovde, E. B., & Ozsarlak‐Sozer, G. (2026) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.70294
“A mutation in the TREM2 gene enhances the inflammatory response and an increase in pro-inflammatory cytokines [136, 137].”
López-Landa, A., González-Sánchez, E., Pérez-Villavicencio, J., García, N. S., García-Hernández, C., Lee, Á., Rubio‐Osornio, M., & Rubio, C. (2026) · Biology · doi:10.3390/biology15201904
Metadata
- Authors
- Roussos, P., Katsel, P., Fam, P., Tan, W., Purohit, D. P., & Haroutunian, V.
- Affiliations
- New York/New Jersey VA Health Care Network (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Haroutunian, Vahram
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2014-12-09
- Volume
- 11
- Issue
- 10
- Pages
- 1163-1170
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC4461564
- OpenAlex
- W2102675610
- Cited by
- 103
- References
- 52
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 11 · 2023: 8 · 2022: 18 · 2021: 8 · 2020: 6 · 2019: 9 · 2018: 9 · 2017: 9 · 2016: 7 · 2015: 3
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P01‐AG02219, P50‐AG05138, MH066392)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- TREM2, Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Brain, Female, Humans, Inflammation, Membrane Glycoproteins, Receptors, Immunologic, Risk, Interleukin-4, Gene Expression, Case-Control Studies, Mutation, Missense, Myeloid Cells, Apolipoprotein E4, Genetic Association Studies, Plaque, Amyloid
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