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Stimulation of TREM2 with agonistic antibodies—an emerging therapeutic option for Alzheimer's disease

Schlepckow, K; Morenas-Rodríguez, E; Hong, S; Haass, C; (2023) Stimulation of TREM2 with agonistic antibodies—an emerging therapeutic option for Alzheimer's disease. The Lancet Neurology , 22 (11) pp. 1048-1060. 10.1016/S1474-4422(23)00247-8. Green open access

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Abstract

Neurodegenerative disorders, including Alzheimer's disease, are associated with microgliosis. Microglia have long been considered to have detrimental roles in Alzheimer's disease. However, functional analyses of genes encoding risk factors that are linked to late-onset Alzheimer's disease, and that are enriched or exclusively expressed in microglia, have revealed unexpected protective functions. One of the major risk genes for Alzheimer's disease is TREM2. Risk variants of TREM2 are loss-of-function mutations affecting chemotaxis, phagocytosis, lipid and energy metabolism, and survival and proliferation. Agonistic anti-TREM2 antibodies have been developed to boost these protective functions in patients with intact TREM2 alleles. Several anti-TREM2 antibodies are in early clinical trials, and current efforts aim to achieve more efficient transport of these antibodies across the blood–brain barrier. PET imaging could be used to monitor target engagement. Data from animal models, and biomarker studies in patients, further support a rationale for boosting TREM2 functions during the preclinical stage of Alzheimer's disease.

Type: Article
Title: Stimulation of TREM2 with agonistic antibodies—an emerging therapeutic option for Alzheimer's disease
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/S1474-4422(23)00247-8
Publisher version: https://doi.org/10.1016/S1474-4422(23)00247-8
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: Animals, Humans, Alzheimer Disease, Microglia, Mutation, Antibodies, Disease Models, Animal, Membrane Glycoproteins, Receptors, Immunologic
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 > UK Dementia Research Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10183624
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