Blood-brain barrier dysfunction and Alzheimer's disease: associations, pathogenic mechanisms, and therapeutic potential

Yanting Chen; Yanfang He; Jinling Han; Wenyan Wei; Feng Chen

doi:10.3389/fnagi.2023.1258640

Blood-brain barrier dysfunction and Alzheimer's disease: associations, pathogenic mechanisms, and therapeutic potential

Front Aging Neurosci. 2023 Nov 13:15:1258640. doi: 10.3389/fnagi.2023.1258640. eCollection 2023.

Authors

Yanting Chen^#¹, Yanfang He^#², Jinling Han¹, Wenyan Wei³, Feng Chen^{2

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Affiliations

¹ Department of Neurology, Shenzhen Sixth People's Hospital, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China.
² Department of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
³ Department of Gerontology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
⁴ Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
⁵ Department of Intensive Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

^# Contributed equally.

Abstract

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ), hyperphosphorylation of tau, and neuroinflammation in the brain. The blood-brain barrier (BBB) limits solutes from circulating blood from entering the brain, which is essential for neuronal functioning. Focusing on BBB function is important for the early detection of AD and in-depth study of AD pathogenic mechanisms. However, the mechanism of BBB alteration in AD is still unclear, which hinders further research on therapeutics that target the BBB to delay the progression of AD. The exact timing of the vascular abnormalities in AD and the complex cause-and-effect relationships remain uncertain. Thus, it is necessary to summarize and emphasize this process. First, in this review, the current evidence for BBB dysfunction in AD is summarized. Then, the interrelationships and pathogenic mechanisms between BBB dysfunction and the risk factors for AD, such as Aβ, tau, neuroinflammation, apolipoprotein E (ApoE) genotype and aging, were analyzed. Finally, we discuss the current status and future directions of therapeutic AD strategies targeting the BBB. We hope that these summaries or reviews will allow readers to better understand the relationship between the BBB and AD.

Keywords: Alzheimer’s disease; aging; apolipoprotein E; blood-brain barrier; neuroinflammation.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Natural Science Foundation of China (82301611), the project funded by the China Postdoctoral Science Foundation (2022M710848) and the Natural Science Foundation of Guangdong Province (2023A1515010179).