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Licensed Unlicensed Requires Authentication Published by De Gruyter July 6, 2022

Immunosenescence of brain accelerates Alzheimer’s disease progression

  • Hou-Yu Chen , Yan Zhao ORCID logo EMAIL logo and Yong-Zhi Xie EMAIL logo

Abstract

Most of Alzheimer’s disease (AD) cases are sporadic and occur after age 65. With prolonged life expectancy and general population aging, AD is becoming a significant public health concern. The immune system supports brain development, plasticity, and homeostasis, yet it is particularly vulnerable to aging-related changes. Aging of the immune system, called immunosenescence, is the multifaceted remodeling of the immune system during aging. Immunosenescence is a contributing factor to various age-related diseases, including AD. Age-related changes in brain immune cell phenotype and function, crosstalk between immune cells and neural cells, and neuroinflammation work together to promote neurodegeneration and age-related cognitive impairment. Although numerous studies have confirmed the correlation between systemic immune changes and AD, few studies focus on the immune state of brain microenvironment in aging and AD. This review mainly addresses the changes of brain immune microenvironment in aging and AD. Specifically, we delineate how various aspects of the brain immune microenvironment, including immune gateways, immune cells, and molecules, and the interplay between immune cells and neural cells, accelerate AD pathogenesis during aging. We also propose a theoretical framework of therapeutic strategies selectively targeting the different mechanisms to restore brain immune homeostasis.


Corresponding authors: Yan Zhao, Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Institute of Aging and Age-related Disease Research, Central South University, Changsha, Hunan 410011, China, E-mail: ; and Yong-Zhi Xie, Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China, E-mail:

Funding source: the Fundamental Research Funds for the Central Universities of Central South University

Award Identifier / Grant number: 2021zzts0359

Funding source: Hunan Provincial Innovation Foundation For Postgraduate

Award Identifier / Grant number: CX20210128

  1. Authors’ contributions: CHY collected the literature and wrote the manuscript. ZY conceived the idea and had been involved in manuscript conception and drafting. XYZ supervised the manuscript and directed the writing. All authors read and approved the final manuscript.

  2. Research funding: This work was supported by the Fundamental Research Funds for the Central Universities of Central South University (No. 2021zzts0359); Hunan Provincial Innovation Foundation For Postgraduate (No. CX20210128).

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Received: 2022-02-25
Accepted: 2022-06-04
Published Online: 2022-07-06
Published in Print: 2023-01-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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