AccScience Publishing / AN / Online First / DOI: 10.36922/AN025310085
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MINI-REVIEW

Nucleolar alterations in brain aging and Alzheimer’s disease

Bin Wu1 ,  Juan Zhang2 ,  Yao Lu1* ,  Qiang Liu3,4,5*
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1 Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Key Laboratory of Anesthesia and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China
2 Department of Pathophysiology, School of Basic Medical Sciences, Wannan Medical College, Wuhu, Anhui, China
3 Hefei National Research Center for Physical Sciences at the Microscale, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
4 Anhui Province Key Laboratory of Biomedical Aging Research, University of Science and Technology of China, Hefei, China
5 Department of Anesthesiology, Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
Advanced Neurology, 025310085 https://doi.org/10.36922/AN025310085
Received: 30 July 2025 | Revised: 15 October 2025 | Accepted: 17 October 2025 | Published online: 10 November 2025
(This article belongs to the Special Issue Advanced Neurology 3rd Anniversary Special Issue)
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The nucleolus is a dynamic, non-membrane-bound nuclear organelle organized into fibrillar and granular components, serving as a central hub for ribosome biogenesis, stress responses, and cell cycle regulation. In brain aging and Alzheimer’s disease (AD), it undergoes marked structural and functional alterations. Aging brains commonly exhibit cognitive decline, whereas AD is characterized by neuronal loss and biochemical abnormalities, including extracellular amyloid-beta plaques and tau hyperphosphorylation. Mounting evidence indicates that nucleolar alterations—such as impaired ribosome biogenesis, disrupted proteostasis, and activation of nucleolar stress pathways—occur early in AD pathogenesis. This review summarizes current understanding of nucleolar function, highlights its dysfunction in aging and AD, and discusses its potential as a therapeutic target.

Keywords
Brain aging
Alzheimer’s disease
Nucleolus
Structure and function
Funding
This work was supported by the National Key R&D Program of China (2021YFA0804900 and 2020YFA0509300), the National Natural Science Foundation of China (82125009, 82330045, 82071185, 92149303, 32121002 and 82470279), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB39000000), CAS Project for Young Scientists in Basic Research (YSBR- 013), Plans for Major Provincial Science & Technology Projects (202303a07020004), Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM (QYZD20220003), the Major Frontier Research Project of the University of Science and Technology of China (LS9100000002), the Hefei Comprehensive National Science Center Hefei Brain Project, and the USTC Research Funds of the Double First-Class Initiative.
Conflict of interest
Qiang Liu is an Editorial Board Member of this journal, but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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