{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:00:10Z","timestamp":1792094410127,"version":"4.4.0"},"reference-count":201,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"US National Institute of Health (NIH)","award":["R21 AI66543"],"award-info":[{"award-number":["R21 AI66543"]}]},{"name":"US National Institute of Health (NIH)","award":["R21 AG069226"],"award-info":[{"award-number":["R21 AG069226"]}]},{"name":"US National Institute of Health (NIH)","award":["R61 AG075725"],"award-info":[{"award-number":["R61 AG075725"]}]},{"name":"US National Institute of Health (NIH)","award":["952272"],"award-info":[{"award-number":["952272"]}]},{"name":"US National Institute of Health (NIH)","award":["R21 AG066060"],"award-info":[{"award-number":["R21 AG066060"]}]},{"name":"TARCC Investigator-Initiated Research Award","award":["R21 AI66543"],"award-info":[{"award-number":["R21 AI66543"]}]},{"name":"TARCC Investigator-Initiated Research Award","award":["R21 AG069226"],"award-info":[{"award-number":["R21 AG069226"]}]},{"name":"TARCC Investigator-Initiated Research Award","award":["R61 AG075725"],"award-info":[{"award-number":["R61 AG075725"]}]},{"name":"TARCC Investigator-Initiated Research Award","award":["952272"],"award-info":[{"award-number":["952272"]}]},{"name":"TARCC Investigator-Initiated Research Award","award":["R21 AG066060"],"award-info":[{"award-number":["R21 AG066060"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Alzheimer\u2019s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe cute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD such as the lytic replication and axonal transport of HSV-1, the various mechanisms of ZIKV neurotropism through the human protein Musashi-1 (MSI1), and the spread of SARS-CoV-2 through the transfer of the virus through the BBB endothelial cells to glial cells and then to neurons via transsynaptic transfer. We will also explore beyond these mere associations by carefully analyzing the potential mechanisms by which these viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, the dysregulation of immune responses, and the impact on protein processing (A\u03b242 and hyperphosphorylated tau). Controversies and challenges of the virus\u2013AD relationship emerge as we tease out these potential mechanisms. Looking forward, we emphasize future directions, such as distinct questions and proposed experimentations to explore, that the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development while encouraging further discussion.<\/jats:p>","DOI":"10.3390\/pathogens13030240","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T10:10:52Z","timestamp":1709892652000},"page":"240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Viral Infections, Are They a Trigger and Risk Factor of Alzheimer\u2019s Disease?"],"prefix":"10.3390","volume":"13","author":[{"given":"Meagan D.","family":"Rippee-Brooks","sequence":"first","affiliation":[{"name":"Microbiology and Immunology Graduate Program, Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8030-3698","authenticated-orcid":false,"given":"Wenzhe","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 77550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianli","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Pappolla","sequence":"additional","affiliation":[{"name":"Department of Neurology and Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX 77550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX 77550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6884-2584","authenticated-orcid":false,"given":"Xiaoyong","family":"Bao","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology Graduate Program, Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77550, USA"},{"name":"Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 77550, USA"},{"name":"The Institute of Translational Sciences, The University of Texas Medical Branch, Galveston, TX 77550, USA"},{"name":"The Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston, TX 77550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.12779\/dnd.2016.15.4.115","article-title":"History of Alzheimer\u2019s Disease","volume":"15","author":"Yang","year":"2016","journal-title":"Dement. 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