CCR5 deficiency: Decreased neuronal resilience to oxidative stress and increased risk of vascular dementia.

As 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. Logistic regression models with CCR5/apolipoprotein E (ApoE) polymorphisms were applied on a sample of 205 cognitively normal individuals and 189 dementia patients from Geneva. The impact of oxidative stress on Ccr5 expression and cell death was assessed in mice neurons. CCR5-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 11-fold greater risk of vascular-and-mixed dementia. Oxidative stress-induced cell death in Ccr5-/- mice neurons. We propose the vulnerability of CCR5-deficient neurons in response to oxidative stress as possible mechanisms contributing to dementia. © 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Citation

Benjamin B Tournier, Silvia Sorce, Antoine Marteyn, Roberta Ghidoni, Luisa Benussi, Giuliano Binetti, François R Herrmann, Karl-Heinz Krause, Dina Zekry. CCR5 deficiency: Decreased neuronal resilience to oxidative stress and increased risk of vascular dementia. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024 Jan;20(1):124-135

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PMID: 37489764

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