Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

作     者：Beibei Wu Yuqing Liu Hongli Li Lemei Zhu Lingfeng Zeng Zhen Zhang Weijun Peng 

作者机构：Department of Integrated Traditional Chinese&Western MedicineThe Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Academician WorkstationChangsha Medical UniversityChangshaHunan ProvinceChina Yangsheng College of Traditional Chinese MedicineGuizhou University of Traditional Chinese MedicineGuiyangGuizhou ProvinceChina Qinhuangdao Shanhaiguan Pharmaceutical Co.LtdQinhuangdaoHebei ProvinceChina National Clinical Research Center for Mental DisorderThe Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2025年第20卷第3期

页      面：695-714页

核心收录：

学科分类：1002[医学-临床医学] 100203[医学-老年医学] 10[医学] 

基　　金：financially supported by the Science and Technology Innovation Program of Hunan Province,No.2022RC1220(to WP) China Postdoctoral Science Foundation,No.2022M711733(to ZZ) the National Natural Science Foundation of China,No.82160920(to ZZ) Hebei Postdoctoral Scientific Research Project,No.B2022003040(to ZZ) Hunan Flagship Department of Integrated Traditional Chinese and Western Medicine(to WP)。 

主　　题：ABCA1 Alzheimer's disease amyloid-beta apolipoprotein E cholesterol metabolism liver liver X receptor low-density lipoprotein receptor-related protein 1 peripheral clearance tauroursodeoxycholic acid 

摘      要：Alzheimer s disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer s disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer s disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer s disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer s disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer s disease.In this review,we explore the underlying causes of Alzheimer s disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer s disease.