Department of Chemistry, Vanderbilt University, Nashville, TN, USA.
Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Adv Exp Med Biol. 2019;1118:1-28. doi: 10.1007/978-3-030-05542-4_1.
Alzheimer's disease (AD) disproportionately affects African Americans (AAs) and Hispanics, who are more likely to have AD than non-Hispanic Whites (NHWs) and Asian Americans. Racial disparities in AD are multifactorial, with potential contributing factors including genetics, comorbidities, diet and lifestyle, education, healthcare access, and socioeconomic status. Interestingly, comorbidities such as hypertension, type 2 diabetes mellitus, and cardiovascular disease also impact AAs. It is plausible that a common underlying molecular basis to these higher incidences of AD and comorbidities exists especially among AAs. A likely common molecular pathway that is centrally linked to AD and these noted comorbidities is alterations in lipid metabolism. Several genes associated with AD risk-most notably, the ε4 allele of the apolipoprotein E (APOE) gene and several mutations in the ATP-binding cassette transporter A7 (ABCA7) gene-are linked to altered lipid metabolism, especially in AAs. This review explores the role of lipid metabolism in AD broadly, as well as in other comorbidities that are prevalent in AAs. Because there are gaps in our understanding of the molecular basis of higher incidences of AD in AAs, 'omics approaches such as proteomics and lipidomics are presented as potential methods to improve our knowledge in these areas.
阿尔茨海默病(AD)在非裔美国人和西班牙裔中不成比例地高发,他们比非西班牙裔白人(NHW)和亚裔美国人更容易患 AD。AD 中的种族差异是多因素的,潜在的促成因素包括遗传、合并症、饮食和生活方式、教育、医疗保健可及性和社会经济地位。有趣的是,合并症如高血压、2 型糖尿病和心血管疾病也会影响非裔美国人。这些更高的 AD 发病率和合并症存在共同的潜在分子基础,尤其是在非裔美国人中,这是合理的。一个可能的共同分子途径与 AD 和这些注意到的合并症密切相关,即脂代谢的改变。几种与 AD 风险相关的基因——最著名的是载脂蛋白 E(APOE)基因的 ε4 等位基因和 ATP 结合盒转运蛋白 A7(ABCA7)基因的几个突变——与脂代谢的改变有关,尤其是在非裔美国人中。本综述广泛探讨了脂代谢在 AD 以及在非裔美国人中普遍存在的其他合并症中的作用。由于我们对非裔美国人中 AD 发病率较高的分子基础的理解存在差距,因此提出了“组学”方法,如蛋白质组学和脂质组学,作为提高我们在这些领域知识的潜在方法。