{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:04:53Z","timestamp":1793822693930,"version":"4.6.1"},"reference-count":383,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) research has transcended the traditional paradigm centered on amyloid-beta (A\u03b2) shifting toward 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 A\u03b2 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\u03b2 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.<\/jats:p>","DOI":"10.3389\/fnagi.2026.1748418","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:42:53Z","timestamp":1772602973000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Emerging pathological mechanisms of Alzheimer\u2019s disease pathogenesis: from neuroimmune interactions to intercellular communication"],"prefix":"10.3389","volume":"18","author":[{"given":"Rutong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, The First People\u2019s Hospital of Xiangtan, Xiangtan","place":["Hunan, China"]},{"name":"Hengyang Medical School, Clinical Anatomy and Reproductive Medicine Application Institute, University of South China, Hengyang","place":["Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingqi","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First People\u2019s Hospital of Xiangtan, Xiangtan","place":["Hunan, China"]},{"name":"Hengyang Medical School, Clinical Anatomy and Reproductive Medicine Application Institute, University of South China, Hengyang","place":["Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First People\u2019s Hospital of Xiangtan, Xiangtan","place":["Hunan, China"]},{"name":"Hengyang Medical School, Clinical Anatomy and Reproductive Medicine Application Institute, University of South China, Hengyang","place":["Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First People\u2019s Hospital of Xiangtan, Xiangtan","place":["Hunan, China"]},{"name":"Hengyang Medical School, Clinical Anatomy and Reproductive Medicine Application Institute, University of South China, Hengyang","place":["Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runze","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First People\u2019s Hospital of Xiangtan, Xiangtan","place":["Hunan, China"]},{"name":"Hengyang Medical School, Clinical Anatomy and Reproductive Medicine Application Institute, University of South China, Hengyang","place":["Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First People\u2019s Hospital of Xiangtan, Xiangtan","place":["Hunan, China"]},{"name":"Hengyang Medical School, Clinical Anatomy and Reproductive Medicine Application Institute, University of South China, Hengyang","place":["Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First People\u2019s Hospital of Xiangtan, Xiangtan","place":["Hunan, China"]},{"name":"Hengyang Medical School, Clinical Anatomy and Reproductive Medicine Application Institute, University of South China, Hengyang","place":["Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First People\u2019s Hospital of Xiangtan, Xiangtan","place":["Hunan, China"]},{"name":"Hengyang Medical School, Clinical Anatomy and Reproductive Medicine Application Institute, University of South China, Hengyang","place":["Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First People\u2019s Hospital of Xiangtan, Xiangtan","place":["Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nrn1824","article-title":"Astrocyte-endothelial interactions at the blood-brain barrier.","volume":"7","author":"Abbott","year":"2006","journal-title":"Nat. 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