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血清铁蛋白水平与路易体痴呆的认知衰退及生物标志物谱相关。

Serum ferritin levels linked to cognitive decline and biomarker profiles in dementia with lewy bodies.

作者信息

Ren Zhihong, Chen Hui, Wu Hao, Ma Ling-Yun, Gan Jinghuan, Liu Shuai, Zhou Feng, Zhang Guili, Ji Yong

机构信息

Department of Neurology, Beijing electric power hospital, Beijing, China.

China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

出版信息

Acta Neurol Belg. 2025 Jun 4. doi: 10.1007/s13760-025-02804-0.

Abstract

OBJECTIVE

Elevated serum ferritin levels have been associated with neurodegenerative diseases, yet their specific role in dementia with Lewy bodies (DLB) remains insufficiently explored.

METHOD

A total of 434 participants were enrolled, including 217 controls, 217 Alzheimer's disease (AD) patients, and 89 DLB patients. Demographic and clinical characteristics, cognitive performance, and neurobehavioral symptoms were evaluated. Serum ferritin levels were stratified into quartiles, and logistic regression models were used to examine the association between ferritin levels and the risk of DLB. Additionally, biomarker profiles of Aβ42, Aβ40, t-tau, and p-tau were analyzed across ferritin quartiles in DLB patients.

RESULTS

DLB patients exhibited the most severe neurobehavioral symptoms (NPI: 11.09 ± 1.24) and significant cognitive impairment (MMSE: 14.16 ± 6.81; MoCA: 9.77 ± 6.20) compared to controls. Higher serum ferritin levels were significantly associated with increased DLB risk, with the highest quartile showing an adjusted odds ratio of 7.58 (95% CI: 2.52-22.81). In DLB patients, ferritin levels were significantly associated with Aβ42 (p < 0.001), with Aβ42 concentrations following a U-shaped distribution across quartiles, suggesting a complex interplay between ferritin and amyloid pathology. Aβ40, t-tau, and p-tau showed weaker or non-significant associations.

CONCLUSION

Elevated serum ferritin levels are strongly associated with an increased risk of DLB and may modulate amyloid pathology, particularly Aβ42. These findings underscore the relevance of iron metabolism in the pathophysiology of DLB and suggest ferritin as a potential biomarker for diagnosis and disease monitoring.

摘要

目的

血清铁蛋白水平升高与神经退行性疾病有关,但其在路易体痴呆(DLB)中的具体作用仍未得到充分研究。

方法

共纳入434名参与者,包括217名对照者、217名阿尔茨海默病(AD)患者和89名DLB患者。评估了人口统计学和临床特征、认知表现及神经行为症状。血清铁蛋白水平被分为四分位数,并使用逻辑回归模型检验铁蛋白水平与DLB风险之间的关联。此外,还分析了DLB患者四分位数铁蛋白水平下的Aβ42、Aβ40、总tau蛋白(t-tau)和磷酸化tau蛋白(p-tau)的生物标志物谱。

结果

与对照者相比,DLB患者表现出最严重的神经行为症状(神经精神量表:11.09±1.24)和显著的认知障碍(简易精神状态检查表:14.16±6.81;蒙特利尔认知评估量表:9.77±6.20)。较高的血清铁蛋白水平与DLB风险增加显著相关,最高四分位数的调整优势比为7.58(95%置信区间:2.52-22.81)。在DLB患者中,铁蛋白水平与Aβ42显著相关(p<0.001),Aβ42浓度在四分位数间呈U形分布,提示铁蛋白与淀粉样蛋白病理之间存在复杂的相互作用。Aβ40、t-tau和p-tau显示出较弱或无显著关联。

结论

血清铁蛋白水平升高与DLB风险增加密切相关,并可能调节淀粉样蛋白病理,尤其是Aβ42。这些发现强调了铁代谢在DLB病理生理学中的相关性,并提示铁蛋白可作为诊断和疾病监测的潜在生物标志物。

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