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The role of TREM2 in Alzheimer's disease and other neurodegenerative disorders

Carmona, S; Zahs, K; Wu, E; Dakin, K; Bras, J; Guerreiro, R; (2018) The role of TREM2 in Alzheimer's disease and other neurodegenerative disorders. Lancet Neurology , 17 (8) pp. 721-730. 10.1016/S1474-4422(18)30232-1. Green open access

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Abstract

Summary 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.

Type: Article
Title: The role of TREM2 in Alzheimer's disease and other neurodegenerative disorders
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/S1474-4422(18)30232-1
Publisher version: https://doi.org/10.1016/S1474-4422(18)30232-1
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences & Neurology, NASU-HAKOLA-DISEASE, AMYOTROPHIC-LATERAL-SCLEROSIS, FLUID SOLUBLE TREM2, BRAIN GENE-EXPRESSION, CELLS 2 TREM2, PARKINSONS-DISEASE, R47H VARIANT, FRONTOTEMPORAL DEMENTIA, RS75932628 ASSOCIATION, MICROGLIAL RESPONSE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10056337
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