CCR5 缺陷：神经元对氧化应激的抵抗力降低，血管性痴呆的风险增加。
CCR5 deficiency: Decreased neuronal resilience to oxidative stress and increased risk of vascular dementia.
机构信息
Department of Psychiatry, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
出版信息
Alzheimers Dement. 2024 Jan;20(1):124-135. doi: 10.1002/alz.13392. Epub 2023 Jul 25.
INTRODUCTION
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.
METHODS
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.
RESULTS
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.
DISCUSSION
We propose the vulnerability of CCR5-deficient neurons in response to oxidative stress as possible mechanisms contributing to dementia.
简介
由于趋化因子受体 5（CCR5）可能在缺血中起作用，我们研究了 CCR5 缺乏、神经元对氧化应激的敏感性与痴呆症发展之间的联系。
方法
我们在来自日内瓦的 205 名认知正常个体和 189 名痴呆症患者的样本中应用了带有 CCR5/载脂蛋白 E（ApoE）多态性的逻辑回归模型。在小鼠神经元中评估了氧化应激对 Ccr5 表达和细胞死亡的影响。
结果
CCR5-Δ32 等位基因与 ApoEε4 协同作用，成为痴呆症的风险因素，特别是具有血管成分的痴呆症。我们在来自意大利的独立队列中证实了这些结果（157 名认知正常和 620 名痴呆症患者）。年龄≥80 岁且携带 ApoEε4/CCR5-Δ32 基因型的患者患血管性和混合性痴呆症的风险增加 11 倍。氧化应激诱导 Ccr5 小鼠神经元中的细胞死亡。
讨论
我们提出 CCR5 缺陷神经元对氧化应激的脆弱性可能是导致痴呆症的机制之一。
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