Microglia-Mediated Neurovascular Unit Dysfunction in Alzheimer’s Disease

Author:

Huang Wenhao1,Xia Qing12,Zheng Feifei1,Zhao Xue1,Ge Fangliang1,Xiao Jiaying1,Liu Zijie1,Shen Yingying1,Ye Ke1,Wang Dayong1345,Li Yanze1345

Affiliation:

1. Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang Province, China

2. Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China

3. Basic Medical Institute, Heilongjiang Medical Science Academy, Harbin, Heilongjiang Province, China

4. Translational Medicine Center of Northern China, Harbin, Heilongjiang Province, China

5. Key Laboratory of Heilongjiang Province for Genetically Modified Animals, Harbin Medical University, Harbin, Heilongjiang Province, China

Abstract

The neurovascular unit (NVU) is involved in the pathological changes in Alzheimer’s disease (AD). The NVU is a structural and functional complex that maintains microenvironmental homeostasis and metabolic balance in the central nervous system. As one of the most important components of the NVU, microglia not only induce blood-brain barrier breakdown by promoting neuroinflammation, the infiltration of peripheral white blood cells and oxidative stress but also mediate neurovascular uncoupling by inducing mitochondrial dysfunction in neurons, abnormal contraction of cerebral vessels, and pericyte loss in AD. In addition, microglia-mediated dysfunction of cellular components in the NVU, such as astrocytes and pericytes, can destroy the integrity of the NVU and lead to NVU impairment. Therefore, we review the mechanisms of microglia-mediated NVU dysfunction in AD. Furthermore, existing therapeutic advancements aimed at restoring the function of microglia and the NVU in AD are discussed. Finally, we predict the role of pericytes in microglia-mediated NVU dysfunction in AD is the hotspot in the future.

Publisher

IOS Press

Subject

Psychiatry and Mental health,Geriatrics and Gerontology,Clinical Psychology,General Medicine,General Neuroscience

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