Differential associations between apolipoprotein E alleles and cerebral myelin content in normative aging.
Differential associations between apolipoprotein E alleles and cerebral myelin content in normative aging.
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DOI：
10.1016/j.neuroimage.2022.118988
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发表时间：
2022-05-01
期刊：
影响因子：
5.7
通讯作者：
Bouhrara M
中科院分区：
文献类型：
--
作者：
Triebswetter C;Kiely M;Khattar N;Ferrucci L;Resnick SM;Spencer RG;Bouhrara M
越来越多的证据表明髓磷脂破坏可能是神经退行性疾病的早期现象，包括阿尔茨海默病（AD）。了解影响髓磷脂合成和分解的因素将对治疗干预措施的发展和评估至关重要。在这项工作中，我们评估了载脂蛋白E （APOE）遗传变异与脑髓磷脂含量之间的关系。定量磁共振成像（qMRI）对年龄在24岁至94岁之间的92名认知功能正常的成年人进行了队列研究。利用先进的qMRI方法，我们测量了APOE ε4或APOE ε2等位基因携带者和ε33基因型个体的全脑髓磷脂水分数（MWF），髓磷脂含量的直接测量指标，以及纵向和横向松弛率（R1和R2），髓磷脂含量的敏感测量指标。自动脑图算法和统计模型用于评估MWF或松弛率与APOE亚型之间的关系，并考虑了几种大脑结构中的混杂变量，包括年龄、性别和种族。结果表明，与非携带者相比，APOE ε2携带者在大多数脑结构中表现出更高的髓磷脂含量，即更高的MWF、R1或R2值，而ε4携带者比非携带者表现出更低的髓磷脂含量趋势。最后，所有qMRI指标均与年龄呈二次型倒u型关系；归因于从青年到中年髓鞘形成的发展，随后髓鞘逐渐丧失。性别和种族对髓鞘形成的影响总体上不显著。这些发现表明个体遗传背景可能影响脑髓磷脂的维持。虽然是初步的，但这项工作为进一步研究阐明APOE基因型与髓鞘形成之间的关系奠定了基础，这可能为治疗或预防AD提供潜在的靶点。
Mounting evidence indicates that myelin breakdown may represent an early phenomenon in neurodegeneration, including Alzheimer’s disease (AD). Understanding the factors influencing myelin synthesis and breakdown will be essential for the development and evaluation of therapeutic interventions. In this work, we assessed associations between genetic variance in apolipoprotein E (APOE) and cerebral myelin content. Quantitative magnetic resonance imaging (qMRI) was performed on a cohort of 92 cognitively unimpaired adults ranging in age from 24 to 94 years. Using advanced qMRI methodology, we measured whole-brain myelin water fraction (MWF), a direct measure of myelin content, as well as longitudinal and transverse relaxation rates (R1 and R2), sensitive measures of myelin content, in carriers of the APOE ε4 or APOE ε2 alleles and individuals with the ε33 genotype. Automated brain mapping algorithms and statistical models were used to evaluate the relationships between MWF or relaxation rates and APOE isoforms, accounting for confounding variables including age, sex, and race, in several cerebral structures. Our results indicate that carriers of APOE ε2 exhibited significantly higher myelin content, that is, higher MWF, R1 or R2 values, in most cerebral structures investigated as compared to noncarriers, while ε4 carriers exhibited trends toward lower myelin content compared to noncarriers. Finally, all qMRI metrics exhibited quadratic, inverted U-shape, associations with age; attributed to the development of myelination from young to middle age followed by progressive loss of myelin afterwards. Sex and race effects on myelination were, overall, nonsignificant. These findings suggest that individual genetic background may influence cerebral myelin maintenance. Although preliminary, this work lays the foundation for further investigations to clarify the relationship between APOE genotype and myelination, which may suggest potential targets in treatment or prevention of AD.
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DOI：
10.1038/s41366-021-00749-x
发表时间：
2021-04
期刊：
International journal of obesity (2005)
影响因子：
--
作者：
Bouhrara M;Khattar N;Elango P;Resnick SM;Ferrucci L;Spencer RG
通讯作者：
Spencer RG
影响因子：
2.5
作者：
Bouhrara M;Reiter DA;Sexton KW;Bergeron CM;Zukley LM;Spencer RG
通讯作者：
Spencer RG
影响因子：
5.7
作者：
Arshad M;Stanley JA;Raz N
通讯作者：
Raz N
影响因子：
3.3
作者：
Bouhrara, Mustapha;Reiter, David A.;Spencer, Richard G.
通讯作者：
Spencer, Richard G.
影响因子：
9.9
作者：
Cohen, RM;Small, C;Sunderland, T
通讯作者：
Sunderland, T