{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T09:04:44Z","timestamp":1784279084694,"version":"3.55.0"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T00:00:00Z","timestamp":1559865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Twenty-six phase III studies on Alzheimer\u2019s disease are ongoing or have been completed in 2018. Most of these studies are targeting amyloid-beta, its production, polymerization, and\/or multiple interactions. None of the amyloid-beta studies seem to affect positively the clinical outcome of patients with Alzheimer\u2019s disease thus far, no matter the advancement of disease. It is time to consider other hypotheses for the pathogenesis of Alzheimer\u2019s disease, including the potential role of human herpes viruses (HHV), and especially HHV1 (herpes simplex virus type 1), HHV3 (varicella zoster virus), HHV6A, and HHV7. With this perspective, we review the scientific evidence and make the case for appropriately powered, prospective, randomized, and controlled studies using an anti-HHV drug, to establish a causal role for HHV in Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1093\/gerona\/glz150","type":"journal-article","created":{"date-parts":[[2019,6,8]],"date-time":"2019-06-08T08:10:54Z","timestamp":1559981454000},"page":"1058-1060","source":"Crossref","is-referenced-by-count":1,"title":["Time for Well-Powered Controlled Prospective Studies to Test a Causal Role for Herpes Viruses in Alzheimer\u2019s Disease Using Antiherpetic Drugs"],"prefix":"10.1093","volume":"75","author":[{"given":"Pascal J","family":"Goldschmidt-Clermont","sequence":"first","affiliation":[{"name":"ALZADY International LLC , Miami, Florida"},{"name":"Leonard M. Miller School of Medicine, University of Miami , Florida"},{"name":"Epiphany Biosciences Inc. , San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred G","family":"Volinsky","sequence":"additional","affiliation":[{"name":"Epiphany Biosciences Inc. , San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P","family":"LaRosa","sequence":"additional","affiliation":[{"name":"Lahey Infectious Disease , Beverly, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Leonard M. Miller School of Medicine, University of Miami , Florida"},{"name":"The John P. Hussman Institute for Human Genomics , Florida"},{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami , Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A","family":"Peri\u00e7ak-Vance","sequence":"additional","affiliation":[{"name":"Leonard M. Miller School of Medicine, University of Miami , Florida"},{"name":"The John P. Hussman Institute for Human Genomics , Florida"},{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami , Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,7]]},"reference":[{"key":"2026071704200851200_CIT0001","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3389\/fncel.2016.00060","article-title":"Editorial: glial cells: managers of neuro-immunity","volume":"10","author":"Barcia","year":"2016","journal-title":"Front Cell Neurosci"},{"key":"2026071704200851200_CIT0002","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.neuron.2018.05.023","article-title":"Multiscale analysis of independent Alzheimer\u2019s cohorts finds disruption of molecular, genetic, and clinical networks by human herpesvirus","volume":"99","author":"Readhead","year":"2018","journal-title":"Neuron"},{"key":"2026071704200851200_CIT0003","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3389\/fnagi.2018.00048","article-title":"Molecular mechanisms for herpes simplex virus type 1 pathogenesis in Alzheimer\u2019s disease","volume":"10","author":"Harris","year":"2018","journal-title":"Front Aging Neurosci"},{"key":"2026071704200851200_CIT0004","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1126\/science.8346443","article-title":"Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer\u2019s disease in late onset families","volume":"261","author":"Corder","year":"1993","journal-title":"Science"},{"key":"2026071704200851200_CIT0005","doi-asserted-by":"crossref","first-page":"5383","DOI":"10.1128\/JVI.00006-06","article-title":"Effect of apolipoprotein E on the cerebral load of latent herpes simplex virus type 1 DNA","volume":"80","author":"Burgos","year":"2006","journal-title":"J Virol"},{"key":"2026071704200851200_CIT0006","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1038\/d41586-018-05719-4","article-title":"The amyloid hypothesis on trial","volume":"559","author":"Makin","year":"2018","journal-title":"Nature"},{"key":"2026071704200851200_CIT0007","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.neuron.2018.06.030","article-title":"Alzheimer\u2019s disease-associated \u03b2-amyloid is rapidly seeded by herpesviridae to protect against brain infection","volume":"99","author":"Eimer","year":"2018","journal-title":"Neuron"},{"key":"2026071704200851200_CIT0008","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1128\/CMR.00102-15","article-title":"Approved antiviral drugs over the past 50 years","volume":"29","author":"De Clercq","year":"2016","journal-title":"Clin Microbiol Rev"},{"key":"2026071704200851200_CIT0009","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s13311-018-0611-x","article-title":"Anti-herpetic medications and reduced risk of dementia in patients with herpes simplex virus infections-a nationwide, population-based cohort study in Taiwan","volume":"15","author":"Tzeng","year":"2018","journal-title":"Neurotherapeutics"},{"key":"2026071704200851200_CIT0010","author":"Chen","year":"2018","journal-title":"J Clin Psychiatry"},{"key":"2026071704200851200_CIT0011","doi-asserted-by":"crossref","first-page":"e1007791","DOI":"10.1371\/journal.pgen.1007791","article-title":"Ancestral origin of ApoE \u03b54 Alzheimer disease risk in Puerto Rican and African American populations","volume":"14","author":"Rajabli","year":"2018","journal-title":"PLoS Genet"},{"key":"2026071704200851200_CIT0012","first-page":"195","article-title":"Alzheimer\u2019s disease drug development pipeline: 2018","volume":"4","author":"Cummings","year":"2018","journal-title":"Alzheimers Dement"},{"key":"2026071704200851200_CIT0013","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1001\/jama.280.7.605","article-title":"Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. 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