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
| Autor: | Vuono, R., Kouli, A., Legault, E. M., Chagnon, L., Allinson, K. S., La Spada, A., Biunno, I., REGISTRY Investigators of the European Huntington’s Disease Network, Romano, S, Barker, R. A., Drouin-Ouellet, J. |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Huntington Disease Association 03 medical and health sciences 0302 clinical medicine Huntington's disease Alzheimer Disease medicine TREM2 media_common.cataloged_instance Humans Myeloid Cells TLR4 Cognitive decline European union Receptors Immunologic Psychiatry Research Articles media_common Membrane Glycoproteins business.industry Genetic variants Brain motor symptoms medicine.disease cognitive decline Toll-Like Receptor 4 030104 developmental biology Huntington Disease Neurology inflammation Myeloid cells Neurology (clinical) business 030217 neurology & neurosurgery Clinical progression Research Article |
| Zdroj: | Movement Disorders |
| ISSN: | 0885-3185 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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