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The role of TREM2 in Alzheimer's disease and other neurodegenerative disorders
Open accessAbstract
Alzheimer's disease is a genetically complex disorder; rare variants in the triggering receptor expressed on myeloid cells 2 (TREM2) gene have been shown to as much as triple an individual's risk of developing Alzheimer's disease. TREM2 is a transmembrane receptor expressed in cells of the myeloid lineage, and its association with Alzheimer's disease supports the involvement of immune and inflammatory pathways in the cause of the disease, rather than as a consequence of the disease. TREM2 variants associated with Alzheimer's disease induce partial loss of function of the TREM2 protein and alter the behaviour of microglial cells, including their response to amyloid plaques. TREM2 variants have also been shown to cause polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy and frontotemporal dementia. Although the low frequency of TREM2 variants makes it difficult to establish robust genotype-phenotype correlations, such studies are essential to enable a comprehensive understanding of the role of TREM2 in different neurological diseases, with the ultimate goal of developing novel therapeutic approaches.
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“Whole-genome analysis led to the identification of relatively rare mutations in TREM2 gene that are associated with a high AD risk.187”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [187]
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Cites
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Macrophage dynamics and the role of TREM2 at the oral mucosal barrier
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Metadata
- Authors
- Carmona, S., Zahs, K., Wu, E., Dakin, K., Bras, J., & Guerreiro, R.
- Affiliations
- UK Dementia Research Institute (GB)
- Alzforum (US)
- Corresponding author
- Guerreiro, Rita
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 17
- Issue
- 8
- Pages
- 721-730
- ISSN
- 1474-4422 (ISSN-L)
- OpenAlex
- W2884070953
- Cited by
- 244
- References
- 107
- Citations by year
- 2026: 13 · 2025: 28 · 2024: 42 · 2023: 38 · 2022: 30 · 2021: 32 · 2020: 28 · 2019: 28 · 2018: 4
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- green
- discovery.ucl.ac.uk
- Licence
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion, other-oa)
- Funders
- Alzheimer's Society
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- TREM2, Alzheimer's disease, neurodegenerative diseases, myeloid cells, microglia, amyloid plaques, neuroinflammation, genetic risk variants, loss-of-function mutations, frontotemporal dementia, genotype-phenotype correlation, therapeutic target
- MeSH terms
- Alzheimer Disease, Humans, Membrane Glycoproteins, Receptors, Immunologic, Neurodegenerative Diseases, Genetic Predisposition to Disease
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