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作者

Ting Yu, Yuanmin Li, Sheng Li, Shuke Nie, Hongyan Feng, Zhentao Zhang, Lanxia Meng

作者单位

Affiliations ¹ Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. ² Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 264000, China. ³ PET-CT/MRI Center, Faculty of Radiology and Nuclear Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China. ⁴ Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. zhentaozhang@whu.edu.cn. ⁵ TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430000, China. zhentaozhang@whu.edu.cn. ⁶ Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. mlx@whu.edu.cn.

刊名

Cellular and molecular life sciences : CMLS

年份

2025

卷号

Vol.83 No.1

页码

5

ISSN

1420-9071

关键词

Alzheimer’s disease Cerebrotendinous xanthomatosis Cholestanol Cognitive decline Tau.

摘要

Cerebrotendinous xanthomatosis is an autosomal recessive lipid storage disease characterized by the accumulation of cholestanol. CTX patients often suffer from cognitive impairment. We found that serum cholestanol levels are higher in Alzheimer's disease patients than in control subjects. Thus, we tested whether cholestanol regulates the pathogenesis of AD. Cholestanol promotes tau fragmentation and hyperphosphorylation by activating asparagine endopeptidase . AEP knockdown alleviates cholesta...更多

Cerebrotendinous xanthomatosis is an autosomal recessive lipid storage disease characterized by the accumulation of cholestanol. CTX patients often suffer from cognitive impairment. We found that serum cholestanol levels are higher in Alzheimer's disease patients than in control subjects. Thus, we tested whether cholestanol regulates the pathogenesis of AD. Cholestanol promotes tau fragmentation and hyperphosphorylation by activating asparagine endopeptidase . AEP knockdown alleviates cholestanol-induced tau fragmentation and phosphorylation. Feeding cholestanol to tau P301S mice aggravates tau pathology and behavioral defects, while knockout of AEP ameliorates cholestanol-induced tau pathology and behavioral defects in tau P301S mice. These results highlight the role of AEP-mediated tau cleavage in cholestanol-induced tau pathology and cognitive decline. The data also identify the potential therapeutic target of AEP in AD, particularly in AD patients with elevated serum cholestanol levels.收起

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