| Autor: |
Benjamin B. Tournier, Silvia Sorce, Antoine Marteyn, Roberta Ghidoni, Luisa Benussi, Giuliano Binetti, François R Herrmann, Karl-Heinz Krause, Dina Zekry |
| Rok vydání: |
2023 |
| Popis: |
IntroductionAs the chemokine receptor5 (CCR5) may play a role in ischemia, we studied the links between CCR5 deficiency, the sensitivity of neurons to oxidative stress, and the development of dementia.MethodsLogistic regression models with CCR5 and ApoE polymorphisms were applied to 205 cognitively normal and 189 dementia patients included in Geneva. The impact of oxidative stress onCcr5expression and cell death was assessed in mice neurons.ResultsCCR5-Δ32 allele synergized with ApoEε4 as risk factor for dementia and specifically for dementia with a vascular component. We confirmed these results in an independent cohort from Italy (157 cognitively normal and 620 dementia). Carriers of the ApoEε4/CCR5-Δ32 genotype aged ≥80 years have an eleven-fold greater risk of vascular and mixed dementia. Oxidative stress induced cell death inCcr5-/-mice neurons.DiscussionWe propose the vulnerability of CCR5-deficient neurons in response to oxidative stress as possible mechanisms contributing to dementia. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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