Wang Xin, Bakulski Kelly M, Karvonen-Gutierrez Carrie A, Park Sung Kyun, Morgan David, Jackson Brian P, Albin Roger L, Paulson Henry L
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States.
Michigan Alzheimer's Disease Center, University of Michigan, Ann Arbor, MI, United States.
Front Aging Neurosci. 2025 May 30;17:1539749. doi: 10.3389/fnagi.2025.1539749. eCollection 2025.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, impacting millions globally. Essential trace elements are implicated in key age-related physiologic processes but have not been fully examined with respect to AD etiology. This study investigates associations between serum levels of essential trace elements (manganese, iron, cobalt, copper, zinc, selenium, and molybdenum) and AD biomarkers (Aβ42, Aβ42/Aβ40 ratio, p-tau181, and total tau) in midlife women.
This cross-sectional study included 194 midlife women (median age = 53.3 years) from the Study of Women's Health Across the Nation, Michigan site. Serum levels of trace elements were measured using inductively coupled plasma-mass spectrometry, and AD biomarkers were quantified using single molecule array assays. Multivariable linear regression models assessed potential associations and Bayesian kernel machine regression (BKMR) was used to account for complex co-exposures and non-linear relationships.
In the multivariable linear regression models, a doubling of serum molybdenum level was associated with 9.4% higher Aβ42/40 ratio (95% CI: 0.8, 18.6%; = 0.03), and a doubling of serum cobalt level with 17.5% higher p-tau181 level (95% CI: 3.1, 33.8%; = 0.02). Copper showed an inverse association with the Aβ42/40 ratio, while zinc was positively associated with the Aβ42/40 ratio, though these associations were marginally significant. BKMR analysis confirmed these associations.
This study identified statistically significant associations of serum molybdenum and cobalt levels with AD biomarkers, suggesting a potential protective effect of molybdenum against Aβ aggregation and exacerbation of pathologic tau phosphorylation by cobalt. These findings underscore the need for further longitudinal studies to explore the role of essential trace elements in AD pathogenesis.
阿尔茨海默病（AD）是一种以认知功能衰退为特征的进行性神经退行性疾病，全球数百万人受其影响。必需微量元素参与了与年龄相关的关键生理过程，但在AD病因方面尚未得到充分研究。本研究调查了中年女性血清中必需微量元素（锰、铁、钴、铜、锌、硒和钼）水平与AD生物标志物（Aβ42、Aβ42/Aβ40比值、p-tau181和总tau蛋白）之间的关联。
这项横断面研究纳入了来自密歇根州全国妇女健康研究的194名中年女性（年龄中位数 = 53.3岁）。使用电感耦合等离子体质谱法测量微量元素的血清水平，并使用单分子阵列分析法定量AD生物标志物。多变量线性回归模型评估潜在关联，并使用贝叶斯核机器回归（BKMR）来考虑复杂的共同暴露和非线性关系。
在多变量线性回归模型中，血清钼水平翻倍与Aβ42/40比值升高9.4%相关（95%置信区间：0.8，18.6%；P = 0.03），血清钴水平翻倍与p-tau181水平升高17.5%相关（95%置信区间：3.1，33.8%；P = 0.02）。铜与Aβ42/40比值呈负相关，而锌与Aβ42/40比值呈正相关，尽管这些关联的显著性较弱。BKMR分析证实了这些关联。
本研究确定了血清钼和钴水平与AD生物标志物之间具有统计学意义的关联，表明钼对Aβ聚集可能具有保护作用，而钴会加剧病理性tau蛋白磷酸化。这些发现强调需要进一步开展纵向研究，以探索必需微量元素在AD发病机制中的作用。
