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

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Abstract

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.

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Funding

This research was funded by the National Natural Science Foundation of China (Grant No. 81702236); the Changsha Municipal Natural Science Foundation (Grant No. kq2202251); the Research Foundation of Education Bureau of Hunan Province, China (Grant No. 20A333, 21B0895, and 20B350); the Natural Science Foundation of Hunan Province, China (Grant No. 2018JJ3363 and 2023JJ30429); the Project for Young Backbone Teachers in Colleges and Universities in Hunan Province (Grant No. [2020]43); the Hunan Province Key Research and Development Program (Grant No. 2020SK2104); the Scientific Research Project of Hunan Provincial Sports Bureau (Grant No. 2021XH008 and 2021XH090); the Postgraduate Scientific Research Project of Hunan Normal University College of Physical Education (Grant No. 202101010 and 202101009); and the Hunan Province College Students Research Learning and Innovative Experiment Project (Grant No. S202210542039).

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  1. Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha, 410012, China

    Ze-Lin Hu, Yang-Qi Yuan, Zhen Tong, Mei-Qing Liao, Shun-Ling Yuan, Ye Jian, Jia-Lun Yang & Wen-Feng Liu

  2. Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha, 410081, China

    Wen-Feng Liu

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ZLH and YQY conceived the topic and designed the outline of this review. ZLH, ZT, and MQL drafted the manuscript and contributed to the literature review and manuscript writing. All authors have contributed to the manuscript revising and editing.

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Hu, ZL., Yuan, YQ., Tong, Z. et al. Reexamining the Causes and Effects of Cholesterol Deposition in the Brains of Patients with Alzheimer’s Disease. Mol Neurobiol 60, 6852–6868 (2023). https://doi.org/10.1007/s12035-023-03529-y

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