{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:36:01Z","timestamp":1790386561232,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Human herpes simplex virus 1 (HSV1) is discussed to induce amyloid\u2010\u03b2 (A\u03b2) accumulation and neurofibrillary tangles of hyperphosphorylated tau (pTau) in Alzheimer's disease (AD) in cell culture and animal models. A\u03b2 appears to be virostatic. We investigated the association between intrathecal antibodies against HSV or cytomegalovirus (CMV) and cerebrospinal fluid (CSF) AD biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A\u03b2<jats:sub>42<\/jats:sub>\/A\u03b2<jats:sub>40<\/jats:sub> ratio, pTau, and tTau were measured in CSF of 117 patients with early AD positive for amyloid pathology (A+) and 30 healthy controls (A\u2010). CSF\u2010to\u2010serum anti\u2010HSV1\/2\u2010IgG antibody indices (AI\u2010IgG<jats:sub>HSV1\/2<\/jats:sub>) and CMV (AI\u2010IgG<jats:sub>CMV<\/jats:sub>) were determined by enzyme\u2010linked immunosorbent assay (ELISA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exclusively in HSV1\u2010seropositive AD, pTau was positively and significantly predicted by AI\u2010IgG<jats:sub>HSV1\/2<\/jats:sub> and negatively by the A\u03b2<jats:sub>42<\/jats:sub>\/A\u03b2<jats:sub>40<\/jats:sub> ratio in both univariate and multivariate regression analyses. Furthermore, a significant and negative interaction between the AI\u2010IgG<jats:sub>HSV1\/2<\/jats:sub> and A\u03b2<jats:sub>42<\/jats:sub>\/A\u03b2<jats:sub>40<\/jats:sub> ratio on pTau was found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The results support the hypothesis that HSV infection contributes to AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>HSV antibody index is positively associated with tau pathology in patients with AD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>HSV antibody index is negatively associated with cerebral FDG metabolism.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Amyloid modulates the association of HSV antibody index with CSF\u2010pTau.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>HSV in AD offers a pathophysiological model connecting tau and amyloid.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12834","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T22:37:45Z","timestamp":1668724665000},"page":"2117-2134","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Herpes simplex virus alters Alzheimer's disease biomarkers \u2010 A hypothesis paper"],"prefix":"10.1002","volume":"19","author":[{"given":"Oliver","family":"Goldhardt","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy School of Medicine Klinikum rechts der Isar Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Freiberger","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy School of Medicine Klinikum rechts der Isar Technical University of Munich  Munich 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