Reexamining the Causes and Effects of Cholesterol Deposition in the Brains of Patients with Alzheimer’s Disease

• Published in: Molecular neurobiology 2023-12, Vol.60 (12), p.6852-6868
• Main Authors: Hu, Ze-Lin, Yuan, Yang-Qi, Tong, Zhen, Liao, Mei-Qing, Yuan, Shun-Ling, Jian, Ye, Yang, Jia-Lun, Liu, Wen-Feng
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Biomedical and Life Sciences; Biomedicine; Blood-brain barrier; Blood-Brain Barrier - pathology; Brain; Brain - metabolism; Cell Biology; Central nervous system; Cholesterol; Cholesterol - metabolism; Homeostasis; Humans; Lipid metabolism; Metabolism; Neurobiology; Neurodegenerative diseases; Neurology; Neurosciences; Oxidative stress; Phosphorylation; Tau protein; β-Amyloid
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-023-03529-y

Alzheimer's disease (AD) is a degenerative disease of the central nervous system. Numerous studies have shown that imbalances in cholesterol homeostasis in the brains of AD patients precede the onset of clinical symptoms. In addition, cholesterol deposition has been observed in the brains of AD patients even though peripheral cholesterol does not enter the brain through the blood‒brain barrier (BBB). Studies have demonstrated that cholesterol metabolism in the brain is associated with many pathological conditions, such as amyloid beta (Aβ) production, Tau protein phosphorylation, oxidative stress, and inflammation. In 2022, some scholars put forward a new hypothesis of AD: the disease involves lipid invasion and its exacerbation of the abnormal metabolism of cholesterol in the brain. In this review, by discussing the latest research progress, the causes and effects of cholesterol retention in the brains of AD patients are analyzed and discussed. Additionally, the possible mechanism through which AD may be improved by targeting cholesterol is described. Finally, we propose that improving the impairments in cholesterol removal observed in the brains of AD patients, instead of further reducing the already impaired cholesterol synthesis in the brain, may be the key to preventing cholesterol deposition and improving the corresponding pathological symptoms.