Sandra Barral, Zikun Yang, Nicole Phillips, Robert C. Barber, Adam M. Brickman, Lawrence S. Honig, Basilio Cieza, Dolly Reyes-Dumeyer, Richard Mayeux, Farid Rajabli, Michael L. Cuccaro, Jeffery M. Vance, Silvia Mejia Arango, Rafael Samper-Ternent, Alejandra Michaels Obregon, Rosa Montesinos, Marcio Soto-Añari, Juan Carlos Duran, Maria Cusicanqui, Ivonne Z. Jimenez Velazquez, Victoria Marca, Maryenela Illanes-Manrique, Mario Cornejo-Olivas, Margaret Pericak-Vance, Rebeca Wong, Sid O'Bryant, Nilton Custodio, Giuseppe Tosto
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Jimenez Velazquez, Victoria Marca, Maryenela Illanes-Manrique, Mario Cornejo-Olivas, Margaret Pericak-Vance, Rebeca Wong, Sid O'Bryant, Nilton Custodio, Giuseppe Tosto","doi":"10.1002/alz.70138","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> BACKGROUND</h3>\n \n <p>Effect of apolipoprotein E (<i>APOE</i>) on Alzheimer's disease and related dementias (ADRD) risk is heterogeneous across populations, with scarce data on Hispanics/Latinos.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p><i>APOE</i> genotype was studied in 12,221 Hispanics/Latinos (per cohort and via metanalysis): Caribbean-Hispanics, Mexicans, Mexican-Americans, and Peruvians/Bolivians. A subsample had longitudinal assessment and plasma p-tau. We tested the modifying effects of global and local ancestries. Results were replicated in an independent Peruvian cohort and brain samples.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p><i>APOE</i> ε4 effect was strongest in Peruvians/Bolivians (odds ratio [OR] = 6.13, 95% confidence interval [CI] = 2.71–13.83), followed by Mexicans (OR = 4.31, 95% CI = 1.58–11.74), Mexican-Americans (OR = 3.06, 95% CI = 2.04–4.59), and Caribbean-Hispanics (OR = 2.22, 95% CI = 1.99–2.48). Meta-analyses showed OR = 2.32 (95% CI = 2.09–2.57) and OR = 0.81 (95% CI = 0.68–0.97) for the ε4 and ε2 allele, respectively. The <i>APOE</i> ε4 effect was replicated independently in Peruvians (OR = 5.06, 95% CI = 2.48–10.70). ε4 carriers displayed higher ADRD conversions and p-tau levels. Global and local ancestries did not modify ADRD risk, and they were associated with Braak stage.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p><i>APOE</i> shows a heterogeneous effect on ADRD risk in our Hispanics/Latinos sample, the largest to date.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>The apolipoprotein E (<i>APOE</i>) ε4 effect is stronger in Peruvians/Bolivians than in other Hispanic/Latino groups.</li>\n \n <li>The strong <i>APOE</i> effect size in Peruvians and Bolivians was replicated in a second independent Peruvian cohort.</li>\n \n <li>Meta-analysis for ε4 and ε2 confirmed a significant association with Alzheimer's disease and related dementias (ADRD).</li>\n \n <li>Global and local ancestry do not modify the association between <i>APOE</i> genotype and ADRD.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70138","citationCount":"0","resultStr":"{\"title\":\"APOE and Alzheimer's disease and related dementias risk among 12,221 Hispanics/Latinos\",\"authors\":\"Sandra Barral, Zikun Yang, Nicole Phillips, Robert C. 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引用次数: 0
摘要
载脂蛋白E （APOE）对阿尔茨海默病和相关痴呆（ADRD）风险的影响在不同人群中是异质性的，关于西班牙裔/拉丁裔的数据很少。方法对12221名西班牙裔/拉丁裔（每个队列并通过荟萃分析）的APOE基因型进行研究：加勒比裔西班牙裔、墨西哥裔、墨西哥裔美国人和秘鲁/玻利维亚人。一个子样本进行了纵向评估和血浆p-tau。我们测试了全球和本地祖先的修正效应。结果在一个独立的秘鲁队列和大脑样本中得到了重复。结果APOE ε4效应在秘鲁/玻利维亚人中最强（优势比[OR] = 6.13, 95%可信区间[CI] = 2.71 ~ 13.83），其次是墨西哥人（OR = 4.31, 95% CI = 1.58 ~ 11.74）、墨西哥裔美国人（OR = 3.06, 95% CI = 2.04 ~ 4.59）和加勒比裔西班牙人（OR = 2.22, 95% CI = 1.99 ~ 2.48）。meta分析显示，ε4和ε2等位基因的OR分别为2.32 （95% CI = 2.09-2.57）和0.81 （95% CI = 0.68-0.97）。APOE ε4效应在秘鲁人中独立存在（OR = 5.06, 95% CI = 2.48 ~ 10.70）。ε4载体的ADRD转化率和p-tau水平较高。全球和本地血统没有改变ADRD风险，它们与Braak阶段有关。在我们的西班牙裔/拉丁裔样本中，APOE显示出对ADRD风险的异质性影响，这是迄今为止最大的。载脂蛋白E (APOE) ε4效应在秘鲁/玻利维亚人群中强于其他西班牙裔/拉丁裔人群。秘鲁人和玻利维亚人的APOE效应在第二个独立的秘鲁队列中得到了重复。对ε4和ε2的荟萃分析证实，ε4和ε2与阿尔茨海默病和相关痴呆（ADRD）有显著关联。全球和本地血统不能改变APOE基因型和ADRD之间的关系。
APOE and Alzheimer's disease and related dementias risk among 12,221 Hispanics/Latinos
BACKGROUND
Effect of apolipoprotein E (APOE) on Alzheimer's disease and related dementias (ADRD) risk is heterogeneous across populations, with scarce data on Hispanics/Latinos.
METHODS
APOE genotype was studied in 12,221 Hispanics/Latinos (per cohort and via metanalysis): Caribbean-Hispanics, Mexicans, Mexican-Americans, and Peruvians/Bolivians. A subsample had longitudinal assessment and plasma p-tau. We tested the modifying effects of global and local ancestries. Results were replicated in an independent Peruvian cohort and brain samples.
RESULTS
APOE ε4 effect was strongest in Peruvians/Bolivians (odds ratio [OR] = 6.13, 95% confidence interval [CI] = 2.71–13.83), followed by Mexicans (OR = 4.31, 95% CI = 1.58–11.74), Mexican-Americans (OR = 3.06, 95% CI = 2.04–4.59), and Caribbean-Hispanics (OR = 2.22, 95% CI = 1.99–2.48). Meta-analyses showed OR = 2.32 (95% CI = 2.09–2.57) and OR = 0.81 (95% CI = 0.68–0.97) for the ε4 and ε2 allele, respectively. The APOE ε4 effect was replicated independently in Peruvians (OR = 5.06, 95% CI = 2.48–10.70). ε4 carriers displayed higher ADRD conversions and p-tau levels. Global and local ancestries did not modify ADRD risk, and they were associated with Braak stage.
DISCUSSION
APOE shows a heterogeneous effect on ADRD risk in our Hispanics/Latinos sample, the largest to date.
Highlights
The apolipoprotein E (APOE) ε4 effect is stronger in Peruvians/Bolivians than in other Hispanic/Latino groups.
The strong APOE effect size in Peruvians and Bolivians was replicated in a second independent Peruvian cohort.
Meta-analysis for ε4 and ε2 confirmed a significant association with Alzheimer's disease and related dementias (ADRD).
Global and local ancestry do not modify the association between APOE genotype and ADRD.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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