Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance
Beibei Wu
Yuqing Liu
Hongli Li
Lemei Zhu
Lingfeng Zeng
Zhen Zhang
Weijun Peng
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.
Keywords：ABCA1Alzheimer's diseaseamyloid-betaapolipoprotein Echolesterol metabolismliverliver X receptorlow-density lipoprotein receptor-related protein 1peripheral clearancetauroursodeoxycholic acid
Publication Date：2025-03-27
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：20( 695-714 )