Eissman Jaclyn M, Ma Yiyi, Qiao Min, Reyes-Dumeyer Dolly, Piriz Angel, Lee Annie J, Lantigua Rafael A, Medrano Martin, Mejia Diones Rivera, Honig Lawrence S, Grodstein Francine, Bennett David A, De Jager Philip L, Dalgard Clifton L, Mayeux Richard, Vardarajan Badri N
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, 10032, USA, Gertrude H. Sergievsky Center, Columbia University, New York, NY, 10032, USA.
Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
medRxiv. 2025 Jul 15:2025.05.22.25328181. doi: 10.1101/2025.05.22.25328181.
Epigenetic clocks can predict pathological aging associated with Alzheimer's disease (AD) risk, albeit findings are mixed regarding if clocks are predictive in blood and in non-European populations. We constructed epigenetic clocks from blood methylation data in 704 older Hispanic adults and tested the association with a clinical diagnosis of AD and plasma biomarker levels. Biological age and age acceleration, the rate of biological aging, were significantly associated with sex, clinical diagnosis, and levels of eight plasma biomarkers, including P-Tau217 levels. Additionally, biomarker associations trended more significant among -ε4 non-carriers. We also identified that methylation levels in CD4 and CD8 T-cell types are associated with biological aging and showed slightly stronger associations in men. We demonstrate that biological aging, in blood, in a Hispanic cohort of both demented and non-demented individuals, can stratify AD risk, predicting plasma biomarker levels even in preclinical disease.
表观遗传时钟可以预测与阿尔茨海默病（AD）风险相关的病理性衰老，尽管关于时钟在血液和非欧洲人群中是否具有预测性的研究结果不一。我们从704名西班牙裔老年成年人的血液甲基化数据构建了表观遗传时钟，并测试了其与AD临床诊断和血浆生物标志物水平的关联。生物年龄和年龄加速（即生物衰老的速率）与性别、临床诊断以及包括P-Tau217水平在内的八种血浆生物标志物水平显著相关。此外，在-ε4非携带者中，生物标志物的关联趋势更为显著。我们还发现，CD4和CD8 T细胞类型中的甲基化水平与生物衰老相关，并且在男性中表现出稍强的关联。我们证明，在患有痴呆症和未患痴呆症的西班牙裔队列中，血液中的生物衰老可以对AD风险进行分层，甚至在临床前疾病阶段就能预测血浆生物标志物水平。
