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Here, we studied the association between HSV-1 and Alzheimer\u2019s disease biomarkers in humans. Our sample included 182 participants at risk of cognitive decline from the Multidomain Alzheimer Preventive Trial who had HSV-1 plasma serology and an amyloid PET scan. Plasma A\u03b242\/40 ratio, neurofilament light chain and p-tau181 were also available for a sub-sample of participants. Multivariate linear regressions were performed and stratified by <jats:italic>APOE4<\/jats:italic> genotype. The median age was 74.0\u00a0years, 85.2% were infected with HSV-1. Infected participants tended to have a lower cortical amyloid load than uninfected participants (\u03b2\u2009=\u2009-0.08, p\u2009=\u20090.06), especially those suspected of reactivating HSV-1 most frequently (i.e. with a high anti-HSV-1 IgG level; n\u2009=\u200958, \u03b2\u2009=\u2009-0.09 p\u2009=\u20090.04). After stratification, the association was only significant in <jats:italic>APOE4<\/jats:italic> carriers (n\u2009=\u200943, \u03b2\u2009=\u2009-0.21 p\u2009=\u20090.01). No association was found with the plasma biomarkers. The trend toward lower cortical amyloid load in HSV-1-infected participants was unexpected given the pre-existing literature and may be explained either by a modified immune response in HSV-1 infected subjects which could favour the clearance of amyloid deposits or by a selection bias.<\/jats:p>","DOI":"10.1038\/s41598-024-84583-x","type":"journal-article","created":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T02:55:21Z","timestamp":1737168921000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Association between herpes simplex virus infection and Alzheimer\u2019s disease biomarkers: analysis within the MAPT trial"],"prefix":"10.1038","volume":"15","author":[{"given":"Morgane","family":"Linard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Garrigue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Vellas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Coley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas James","family":"Ashton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Payoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Sophie","family":"Salabert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Dartigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Mazere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Andrieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Helmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,18]]},"reference":[{"key":"84583_CR1","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1016\/j.nicl.2013.02.006","volume":"2","author":"G Ch\u00e9telat","year":"2013","unstructured":"Ch\u00e9telat, G. et al. 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