REVIEW article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Emerging Pathological Mechanisms of Alzheimer's Disease Pathogenesis: From Neuroimmune Interactions to Intercellular Communication
Rutong Wang 1,2
Yingqi Feng 1,2
Ziyu Zhou 1,2
Jiajun Jiang 1,2
Runze Zhang 1,2
Wenhui Zou 1,2
Haotian Yang 1,2
Wenbo Lv 1,2
Shen Yang 1
1. The First People's Hospital of Xiangtan City, Xiangtan, China
2. Hengyang Medical College, University of South China, Hengyang, China
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Abstract
Abstract Alzheimer's disease (AD) research has transcended the traditional paradigm centered on amyloid-beta (Aβ) shifting towards a neuroimmune network perspective. This article systematically elucidates the evolving mechanisms underlying disease progression, from neuroimmune interactions to intercellular communication. Studies indicate that microglial and astrocytic dysfunctions are key contributors to disease progression, operating within a complex multifactorial framework. Upon transformation into disease-associated microglia (DAM), microglia exhibit a significant decline in Aβ clearance capacity and release a plethora of pro-inflammatory factors, exacerbating neuroinflammation and neuronal damage. Concurrently, astrocytes lose their homeostatic support functions and acquire neurotoxic properties. Intercellular communication molecules play pivotal roles as key mediators. The cytokine/chemokine network sustains a chronic inflammatory milieu; extracellular vesicles (EVs) facilitate the propagation of A β and tau pathologies; and the complement system (e.g., C1q) transitions from physiological synaptic pruning to pathological synaptic engulfment. Furthermore, peripheral immune cell infiltration and gut-brain axis dysregulation further expand the pathological scope. Consequently, therapeutic strategies are evolving towards multi-target interventions, including precise immune modulation (e.g., TREM2 agonists), exosome-based drug delivery systems, and combination therapies. Addressing disease heterogeneity and developing personalized treatments are critical future directions. Ultimately, early interventions aimed at restoring healthy intercellular communication offer new hope for halting AD progression.
Summary
Keywords
Alzheimer's disease (AD), complement system, extracellular vesicles, Microglia, neuroimmunology
Received
17 November 2025
Accepted
18 February 2026
Copyright
© 2026 Wang, Feng, Zhou, Jiang, Zhang, Zou, Yang, Lv and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Rutong Wang; Shen Yang
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.