{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:01:41Z","timestamp":1789992101276,"version":"4.0.1"},"reference-count":206,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009647","name":"Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009647","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Alzheimer\u2019s disease (AD) is the most common neurodegenerative disorder in older adults, characterized by progressive cognitive decline that ultimately leads to severe dementia. The primary pathophysiological hallmarks of AD include the accumulation of amyloid-\u03b2 plaques, neurofibrillary tangles composed of hyperphosphorylated tau protein, synaptic dysfunction, and pronounced neuroinflammation. Although the exact relationship between neuroinflammation and AD pathogenesis remains incompletely understood, neuroinflammation is consistently recognized as an early and sustained feature of the disease. Accumulating evidence suggests that microbial infections, such as herpes simplex virus type 1, varicella-zoster virus, and\n                    <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                    , may play a role in the etiology and progression of AD and its associated neuroinflammatory processes. The gut microbiota may also contribute to AD pathogenesis through a complex communication network known as the microbiota\u2013gut\u2013brain axis. Dysbiosis, defined as an imbalance in the gut microbial community, may promote AD development and progression by enhancing neuroinflammation and producing microbial-derived toxic metabolites that can impair brain function. Neuroinflammation, in turn, contributes to the disruption of blood\u2013brain barrier integrity, thereby facilitating the infiltration of peripheral immune cells and pathogens into the central nervous system. Importantly, chronic infections may lead to sustained immune activation, establishing a vicious cycle that further amplifies neuroinflammation, thus potentially accelerating AD progression. Emerging evidence highlights the interplay between systemic infections, immune dysregulation, and neurodegenerative processes, suggesting that pathogen-driven inflammation may represent a modifiable risk factor and a potential therapeutic target in AD. In this review, we examine the putative role of infectious pathogens in the development and progression of AD, with particular emphasis on the molecular pathways and key mediators involved in pathogen-triggered neuroinflammation.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1919289","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:07:17Z","timestamp":1789988837000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the role of infectious pathogens in Alzheimer\u2019s disease neuroinflammation"],"prefix":"10.3389","volume":"16","author":[{"given":"Salvatore","family":"Vaiasicca","sequence":"first","affiliation":[{"name":"Center of Biogerontology, IRCCS INRCA","place":["Ancona, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianmarco","family":"Mangiaterra","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, Biotechnology section","place":["Fano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Citterio","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, Biotechnology section","place":["Fano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Piccioni","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, Biotechnology section","place":["Fano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorenza","family":"Orlando","sequence":"additional","affiliation":[{"name":"Experimental Animal Models for Aging Unit, Scientific Technological Area, IRCCS INRCA, Falconara","place":["Marittima, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda","family":"Giorgetti","sequence":"additional","affiliation":[{"name":"Center of Biogerontology, IRCCS INRCA","place":["Ancona, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Cianfruglia","sequence":"additional","affiliation":[{"name":"Center of Biogerontology, IRCCS INRCA","place":["Ancona, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robertina","family":"Giacconi","sequence":"additional","affiliation":[{"name":"Center of Biogerontology, IRCCS INRCA","place":["Ancona, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Fumarola","sequence":"additional","affiliation":[{"name":"Center of Biogerontology, IRCCS INRCA","place":["Ancona, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Cardelli","sequence":"additional","affiliation":[{"name":"Center of Biogerontology, IRCCS INRCA","place":["Ancona, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Biscetti","sequence":"additional","affiliation":[{"name":"Neurology Unit, IRCCS INRCA","place":["Ancona, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Pelliccioni","sequence":"additional","affiliation":[{"name":"Ophthalmology Department, AST Pesaro Urbino","place":["Pesaro, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Casoli","sequence":"additional","affiliation":[{"name":"Center of Biogerontology, IRCCS INRCA","place":["Ancona, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Pelliccioni","sequence":"additional","affiliation":[{"name":"Neurology Unit, IRCCS INRCA","place":["Ancona, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1347987","article-title":"The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets","volume":"16","author":"Adamu","year":"2024","journal-title":"Front. 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