Alzheimer Disease & Associated Disorders ( IF 1.8 ) Pub Date : 2020-07-01 , DOI: 10.1097/wad.0000000000000367 Kevin J Wojta 1 , Ariane H Ayer 1 , Eliana M Ramos 1 , Peter D Nguyen 1 , Anna M Karydas 2 , Jennifer S Yokoyama 2 , Joel Kramer 2 , Suzee E Lee 2 , Adam Boxer 2 , Bruce L Miller 2 , Giovanni Coppola 1
Objective:
Recent studies have suggested that diminished Ccr5 functioning has an effect on synaptic plasticity and hippocampal memory in mouse models. CCR5-delta32, a 32-bp frameshift deletion in human CCR5 encoding a nonfunctional receptor, has been reported to have a protective effect against human immunodeficiency virus infection but its role as a modifier of neurodegenerative disease has been minimally explored. We investigated whether the CCR5-delta32 polymorphism could have an effect in the context of human neurodegenerative diseases.
Methods:
We examined the frequency of the CCR5-delta32 polymorphism in a large and well-characterized cohort including 1425 patients with neurodegenerative dementias and 2032 controls.
Results:
We did not observe a significant association between the CCR5-delta32 polymorphism and any of the neurodegenerative diseases screened in this study. However, we observed an earlier age of onset among neurodegenerative disease patients carrying the CCR5-delta32 allele.
Conclusions:
Although our findings were inconclusive, the earlier age of onset observed among neurodegenerative disease patients carrying the CCR5-delta32 allele suggests that the deletion may have a detrimental effect in the context of neurodegeneration.
中文翻译:
CCR5-delta32 多态性与神经退行性疾病之间缺乏关联。
客观的:
最近的研究表明,减少的Ccr5功能对小鼠模型中的突触可塑性和海马记忆有影响。CCR5 -delta32 是人类CCR5中编码非功能性受体的 32 bp 移码缺失,据报道它对人类免疫缺陷病毒感染具有保护作用,但其作为神经退行性疾病的调节剂的作用尚未得到充分探索。我们研究了CCR5 -delta32 多态性是否会在人类神经退行性疾病的背景下产生影响。
方法:
我们检查了CCR5 -delta32 多态性在一个大型且特征明确的队列中的频率,该队列包括 1425 名神经退行性痴呆患者和 2032 名对照。
结果:
我们没有观察到CCR5 -delta32 多态性与本研究中筛选的任何神经退行性疾病之间的显着关联。然而,我们观察到携带CCR5 -delta32 等位基因的神经退行性疾病患者发病年龄较早。
结论:
尽管我们的研究结果尚无定论,但在携带CCR5 -delta32 等位基因的神经退行性疾病患者中观察到的较早发病年龄表明该缺失可能在神经退行性疾病的背景下产生不利影响。