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肝功能与阿尔茨海默病脑部病变:一项纵向研究:肝脏与阿尔茨海默病病变

Liver function and Alzheimer's brain pathologies: A longitudinal study: Liver and Alzheimer's pathologies.

作者信息

Kim Jee Wook, Byun Min Soo, Yi Dahyun, Jung Joon Hyung, Kong Nayeong, Chang Yoon Young, Jung Gijung, Ahn Hyejin, Lee Jun-Young, Kang Koung Mi, Sohn Chul-Ho, Lee Yun-Sang, Kim Yu Kyeong, Lee Dong Young

机构信息

Department of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, 7 Keunjaebong-gil, Hwaseong, Gyeonggi, 18450, Republic of Korea; Department of Psychiatry, Hallym University College of Medicine, Chuncheon, Gangwon, 24252, Republic of Korea.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, 03080, Republic of Korea; Department of Psychiatry, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.

出版信息

J Prev Alzheimers Dis. 2025 Jan;12(1):100012. doi: 10.1016/j.tjpad.2024.100012. Epub 2025 Jan 1.

Abstract

IMPORTANCE

The neuropathological links underlying the association between changes in liver function and AD have not yet been clearly elucidated.

OBJECTIVE

We aimed to examine the relationship between liver function markers and longitudinal changes in Alzheimer's disease (AD) core pathologies.

DESIGN

Data from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, a longitudinal cohort study initiated in 2014, were utilized.

SETTING

Community and memory clinic setting.

PARTICIPANTS

Three hundred forty-seven older adults.

MAIN OUTCOME AND MEASURES

Participants underwent baseline and 2-year follow-up evaluations, including liver function assessments and various brain imaging techniques, such as amyloid and tau PET, FDG-PET, and MRI). Liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin] were examined as exposure variables.

RESULTS

Higher baseline ALT levels were associated with a greater increase in beta-amyloid deposition over 2 years [β = 0.166, Bonferroni-corrected P (P) = 0.012], while lower total bilirubin levels were associated with a greater increase in tau deposition over the same period (β = -0.570, P < 0.001). In contrast, AST alone showed no significant association with changes of AD pathologies.

CONCLUSIONS AND RELEVANCE

The findings suggest a possible link between lower liver function and the accumulation of core AD pathologies in the brain. These results also support the possibility that the liver-brain axis could be a potential target for therapeutic or preventive strategies against AD.

摘要

重要性

肝功能变化与阿尔茨海默病(AD)之间关联背后的神经病理学联系尚未明确阐明。

目的

我们旨在研究肝功能标志物与阿尔茨海默病(AD)核心病理学纵向变化之间的关系。

设计

利用了韩国阿尔茨海默病早期诊断与预测脑老化研究的数据,这是一项于2014年启动的纵向队列研究。

设置

社区和记忆诊所环境。

参与者

347名老年人。

主要结局和测量指标

参与者接受了基线和2年的随访评估,包括肝功能评估以及各种脑成像技术,如淀粉样蛋白和tau蛋白PET、FDG - PET和MRI)。肝功能指标[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和总胆红素]作为暴露变量进行检测。

结果

较高的基线ALT水平与2年内β - 淀粉样蛋白沉积的更大增加相关[β = 0.166,Bonferroni校正P值(P)= 0.012],而较低的总胆红素水平与同期tau蛋白沉积的更大增加相关(β = -0.570,P < 0.001)。相比之下,单独的AST与AD病理学变化无显著关联。

结论及相关性

研究结果表明肝功能降低与大脑中AD核心病理学积累之间可能存在联系。这些结果也支持肝 - 脑轴可能成为AD治疗或预防策略潜在靶点的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be7/12065704/87523d91ac54/nihms-2076898-f0001.jpg

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