机构：[1]Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China[2]Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China[3]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, National Center for Neurological Disorders, Capital Medical University, Beijing, China神经科系统神经内科首都医科大学宣武医院[4]Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China[5]Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, China
Liver function has been suggested as a possible factor in the progression of Alzheimer's disease (AD) development. However, the association between liver function and cerebrospinal fluid (CSF) levels of AD biomarkers remains unclear. In this study, we analyzed the data from 1687 adults without dementia from the Chinese Alzheimer's Biomarker and LifestylE study to investigate differences in liver function between pathological and clinical AD groups, as defined by the 2018 National Institute on Aging-Alzheimer's Association Research Framework. We also examined the linear relationship between liver function, CSF AD biomarkers, and cognition using linear regression models. Furthermore, mediation analyses were applied to explore the potential mediation effects of AD pathological biomarkers on cognition. Our findings indicated that, with AD pathological and clinical progression, the concentrations of total protein (TP), globulin (GLO), and aspartate aminotransferase/alanine transaminase (ALT) increased, while albumin/globulin (A/G), adenosine deaminase, alpha-L-fucosidase, albumin, prealbumin, ALT, and glutamate dehydrogenase (GLDH) concentrations decreased. Furthermore, we also identified significant relationships between TP (beta = -0.115, p(FDR) < 0.001), GLO (beta = -0.184, p(FDR) < 0.001), and A/G (beta = 0.182, p(FDR) < 0.001) and CSF beta-amyloid(1-42) (A beta(1-42)) (and its related CSF AD biomarkers). Moreover, after 10 000 bootstrapped iterations, we identified a potential mechanism by which TP and GLDH may affect cognition by mediating CSF AD biomarkers, with mediation effect sizes ranging from 3.91% to 16.44%. Overall, our results suggested that abnormal liver function might be involved in the clinical and pathological progression of AD. Amyloid and tau pathologies also might partially mediate the relationship between liver function and cognition. Future research is needed to fully understand the underlying mechanisms and causality to develop an approach to AD prevention and treatment approach. We have included 1687 non-demented participants from the CABLE study and observed the associations between liver function and cerebrospinal fluid biomarkers of Alzheimer's disease.image
基金：
Excellence 2025 Talent CultivationProgram at Fudan University; Science and Technology Innovation [2022ZD0211600]; National Natural Science Foundation of China [82071201, 91849126]; Shanghai Municipal Science and Technology Major Project [2018SHZDZX01]; Research Start-Up Fund of Hua shanHospital [2022QD002]; Shanghai Talent Development Funding for The Proiect [2019074]; [3030277001]
第一作者机构：[1]Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China[2]Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China[*1]National Center for Neurological Diseases in China, Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai 200040, China.[*2]Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China.
推荐引用方式(GB/T 7714)：
Gao Pei-Yang,Ou Ya-Nan,Huang Yi-Ming,et al.Associations between liver function and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in non-demented adults: The CABLE study[J].JOURNAL OF NEUROCHEMISTRY.2024,168(1):39-51.doi:10.1111/jnc.16025.
APA：
Gao, Pei-Yang,Ou, Ya-Nan,Huang, Yi-Ming,Wang, Zhi-Bo,Fu, Yan...&Yu, Jin-Tai.(2024).Associations between liver function and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in non-demented adults: The CABLE study.JOURNAL OF NEUROCHEMISTRY,168,(1)
MLA：
Gao, Pei-Yang,et al."Associations between liver function and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in non-demented adults: The CABLE study".JOURNAL OF NEUROCHEMISTRY 168..1(2024):39-51
