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Genetic risk of dementia modifies obesity effects on white matter myelin in cognitively healthy adults.
Neurobiology of Aging ( IF 3.7 ) Pub Date : 2020-10-01 , DOI: 10.1016/j.neurobiolaging.2020.06.014
Jilu P Mole 1 , Fabrizio Fasano 2 , John Evans 1 , Rebecca Sims 3 , Derek A Hamilton 4 , Emma Kidd 5 , Claudia Metzler-Baddeley 1
Affiliation  

APOE-ε4 is a major genetic risk factor for late-onset Alzheimer's disease that interacts with other risk factors, but the nature of such combined effects remains poorly understood. We quantified the impact of APOE-ε4, family history (FH) of dementia, and obesity on white matter (WM) microstructure in 165 asymptomatic adults (38-71 years old) using quantitative magnetization transfer and neurite orientation dispersion and density imaging. Microstructural properties of the fornix, parahippocampal cingulum, and uncinate fasciculus were compared with those in motor and whole-brain WM regions. Widespread interaction effects between APOE, FH, and waist-hip ratio were found in the myelin-sensitive macromolecular proton fraction from quantitative magnetization transfer. Among individuals with the highest genetic risk (FH+ and APOE-ε4), obesity was associated with reduced macromolecular proton fraction in the right parahippocampal cingulum, whereas no effects were present for those without FH. Risk effects on apparent myelin were moderated by hypertension and inflammation-related markers. These findings suggest that genetic risk modifies the impact of obesity on WM myelin consistent with neuroglia models of aging and late-onset Alzheimer's disease.

中文翻译:


痴呆症的遗传风险改变了肥胖对认知健康成年人白质髓磷脂的影响。



APOE-ε4 是晚发性阿尔茨海默病的一个主要遗传风险因素,它与其他风险因素相互作用,但这种综合效应的性质仍然知之甚少。我们使用定量磁化转移、神经突定向弥散和密度成像,量化了 APOE-ε4、痴呆家族史 (FH) 和肥胖对 165 名无症状成年人(38-71 岁)白质 (WM) 微结构的影响。将穹窿、海马旁扣带回和钩束的微观结构特性与运动和全脑 WM 区域的微观结构特性进行比较。在定量磁化转移的髓磷脂敏感大分子质子分数中发现了 APOE、FH 和腰臀比之间广泛的相互作用效应。在遗传风险最高的个体(FH+和APOE-ε4)中,肥胖与右侧海马旁扣带回大分子质子分数的降低有关,而对于没有FH的个体则没有影响。对表观髓磷脂的风险影响受到高血压和炎症相关标志物的调节。这些发现表明,遗传风险改变了肥胖对 WM 髓磷脂的影响,这与衰老和迟发性阿尔茨海默病的神经胶质细胞模型一致。
更新日期:2020-10-01
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