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Association Between Toll‐Like Receptor 4 ( TLR4 ) and Triggering Receptor Expressed on Myeloid Cells 2 ( TREM2 ) Genetic Variants and Clinical Progression of Huntington's Disease

Vuono, Romina, Kouli, Antonina, Legault, Emilie M., Chagnon, Lauriane, Allinson, Kieren S., La Spada, Alberto, Biunno, Ida, Barker, Roger A., Drouin‐Ouellet, Janelle (2020) Association Between Toll‐Like Receptor 4 ( TLR4 ) and Triggering Receptor Expressed on Myeloid Cells 2 ( TREM2 ) Genetic Variants and Clinical Progression of Huntington's Disease. Movement Disorders, 35 (3). pp. 401-408. ISSN 0885-3185. (doi:10.1002/mds.27911) (KAR id:78968)

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Abstract

Background: Although Huntington's disease (HD) is caused by a single dominant gene, it is clear that there are genetic modifiers that may influence the age of onset and disease progression.

Objectives: We sought to investigate whether new inflammation‐related genetic variants may contribute to the onset and progression of HD. Methods: We first used postmortem brain material from patients at different stages of HD to look at the protein expression of toll‐like receptor 4 (TLR4) and triggering receptor expressed on myeloid cells 2 (TREM2). We then genotyped the TREM2 R47H gene variant and 3 TLR4 single nucleotide polymorphisms in a large cohort of HD patients from the European Huntington's Disease Network REGISTRY. Results: We found an increase in the number of cells expressing TREM2 and TLR4 in postmortem brain samples from patients dying with HD. We also found that the TREM2 R47H gene variant was associated with changes in cognitive decline in the large cohort of HD patients, whereas 2 of 3 TLR4 single nucleotide polymorphisms assessed were associated with changes in motor progression in this same group. Conclusions: These findings identify TREM2 and TLR4 as potential genetic modifiers for HD and suggest that inflammation influences disease progression in this condition. © 2019 International Parkinson and Movement Disorder Society

Item Type: Article
DOI/Identification number: 10.1002/mds.27911
Uncontrolled keywords: cognitive decline, Huntington, inflammation, motor symptoms, TLR4, TREM2
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Romina Vuono
Date Deposited: 25 Nov 2019 15:18 UTC
Last Modified: 04 Jul 2023 13:47 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/78968 (The current URI for this page, for reference purposes)

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