Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (3): 695-714.doi: 10.4103/1673-5374.391305

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

Beibei Wu1 , Yuqing Liu1 , Hongli Li1 , Lemei Zhu2 , Lingfeng Zeng2 , Zhen Zhang1, 3, 4, *, Weijun Peng1, 5, *   

  1. 1 Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China; 2 Academician Workstation, Changsha Medical University, Changsha, Hunan Province, China; 3 Yangsheng College of Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, China; 4 Qinhuangdao Shanhaiguan Pharmaceutical Co., Ltd, Qinhuangdao, Hebei Province, China; 5 National Clinical Research Center for Mental Disorder, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
  • Online:2025-03-15 Published:2024-06-25
  • Contact: Zhen Zhang, PhD, zhangzhen035@gzy.edu.cn; Weijun Peng, PhD, pengweijun87@csu.edu.cn.
  • Supported by:
    This work was 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); and Hunan Flagship Department of Integrated Traditional Chinese and Western Medicine (to WP).

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Abstract: 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.

Key words: 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